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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 145 records · Page 8
All sourcesNASA NTRSDOE OSTI
NASA NTRS2000

The actin cytoskeleton may control the polar distribution of an auxin transport protein

The gravitropic bending of plants has long been linked to the changes in the transport of the plant hormone auxin. To understand the mechanism by which gravity alters auxin movement, it is critical to know how polar auxin transport is initially established. In shoots, polar auxin transport is basipetal (i.e., from the shoot apex toward the base). It is driven by the basal localization of the auxin efflux carrier complex. One mechanism for localizing this efflux carrier complex to the basal membrane may be through attachment to the actin cytoskeleton. The efflux carrier protein complex is believed to consist of several polypeptides, including a regulatory subunit that binds auxin transport inhibitors, such as naphthylphthalamic acid (NPA). Several lines of experimentation have been used to determine if the NPA binding protein interacts with actin filaments. The NPA binding protein has been shown to partition with the actin cytoskeleton during detergent extraction. Agents that specifically alter the polymerization state of the actin cytoskeleton change the amount of NPA binding protein and actin recovered in these cytoskeletal pellets. Actin-affinity columns were prepared with polymers of actin purified from zucchini hypocotyl tissue. NPA binding activity was eluted in a single peak from the actin filament column. Cytochalasin D, which fragments the actin cytoskeleton, was shown to reduce polar auxin transport in zucchini hypocotyls. The interaction of the NPA binding protein with the actin cytoskeleton may localize it in one plane of the plasma membrane, and thereby control the polarity of auxin transport.

Non-NASA Center↗
DOE OSTI2020

SERTA Domain Containing Protein 1 (SERTAD1) Interacts with Classical Swine Fever Virus Structural Glycoprotein E2, Which Is Involved in Virus Virulence in Swine

E2 is the major structural glycoprotein of the classical swine fever virus (CSFV). E2 has been shown to be involved in important virus functions such as replication and virulence in swine. Using the yeast two-hybrid system, we previously identified several host proteins specifically interacting with CSFV E2. Here, we analyze the protein interaction of E2 with SERTA domain containing protein 1 (SERTAD1), a factor involved in the stimulation of the transcriptional activities of different host genes. We have confirmed that the interaction between these two proteins occurs in CSFV-infected swine cells by using a proximity ligation assay and confocal microscopy. Amino acid residues in the CSFV E2 protein that are responsible for mediating the interaction with SERTAD1 were mapped by a yeast two-hybrid approach using a randomly mutated E2 library. Using that information, a recombinant CSFV mutant (E2ΔSERTAD1v) that harbors substitutions in those residues mediating the protein-interaction with SERTAD1 was developed and used to study the role of the E2-SERTAD1 interaction in viral replication and virulence in swine. CSFV E2ΔSERTAD1v, when compared to the parental BICv, showed a clearly decreased ability to replicate in the SK6 swine cell line and a more severe replication defect in primary swine macrophage cultures. Importantly, 80% of animals infected with E2ΔSERTAD1v survived infection, remaining clinically normal during the 21-day observational period. This result would indicate that the ability of CSFV E2 to bind host SERTAD1 protein during infection plays a critical role in virus virulence.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

LxCxD motif of the APC/C coactivator subunit FZR1 is critical for interaction with the retinoblastoma protein

Highlights: • Several oncogenic viral proteins bind to tumor suppressor pRB via LxCxE motif. • LxCxE present in many cellular proteins that interact with pRB. • APC/C interacts with pRB via this motif in its FZR1 subunit. • FZR1 LxCxE-like LxCxD critical for FZR1-pRB direct binding and SKP2 ubiquitylation. • Mutation of FZR1 LxCxD alters cell cycle. Retinoblastoma protein (pRB) regulates cell cycle by utilizing different regions of its pocket domain for interacting with E2F family of transcription factors and with cellular and viral proteins containing an LxCxE motif. An LxCxE-like motif, LxCxD, is present in FZR1, an adaptor protein of the multi-subunit E3 ligase complex anaphase-promoting complex/cyclosome (APC/C). The APC/C{sup FZR1} complex regulates the timely degradation of multiple cell cycle proteins for mitotic exit and maintains G1 state. We report that FZR1 interacts with pRB via its LxCxD motif. By using point mutations, we found that the cysteine residue in the FZR1 LxCxD motif is critical for direct interaction with pRb. The direct binding of the LxCxD motif of FZR1 to the pRB LxCxE binding pocket is confirmed by using human papillomavirus protein E7 as a competitor, both in vitro and in vivo. While mutation of the cysteine residue significantly disrupts FZR1 interaction with pRB, this motif does not affect FZR1 and core APC/C association. Expression of the FZR1 point mutant results in accumulation of S-phase kinase-associated protein 2 (SKP2) and Polo-like kinase 1 (PLK1), while p27{sup Kip1} and p21{sup Cip1} proteins are downregulated, indicating a G1 cell cycle defect. Consistently, cells containing point mutant FZR1 enter the S phase prematurely. Together our results suggest that the LxCxD motif of FZR1 is a critical determinant for the interaction between FZR1 and pRB and is important for G1 restriction.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Changes in the C-terminal, N-terminal, and histidine regions of amelogenin reveal the role of oligomer quaternary structure on adsorption and hydroxyapatite mineralization

Adsorption interactions between amelogenin and calcium phosphate minerals are believed to be important to amelogenin’s function in enamel formation, however, the role of specific amino acid residues and domains within the protein in controlling adsorption is not well known. We synthesized “mechanistic probes” by systematically removing charged regions of amelogenin in order to elucidate their roles. The probes included amelogenin without the charged residues in the N-terminus (SEKR), without two, three, or eight histidines (H) in the central protein region (H2, H3, H8), or without the C-terminal residues (Delta). In-situ atomic force microscopy (AFM) adsorption studies onto hydroxyapatite (HAP) single crystals confirmed that the C-terminus was the dominant domain in promoting adsorption. We propose that subtle changes in protein-protein interactions for proteins with histidines and N-terminal residues removed resulted in changes in the oligomer quaternary size and structure that also affected protein adsorption. HAP mineralization studies revealed that the oligomer-HAP binding energy and protein layer thickness were factors in controlling the amorphous calcium phosphate (ACP) to HAP induction time. Our studies with mechanistic probes reveal the importance of the oligomer quaternary structure in controlling amelogenin adsorption and HAP mineralization.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Catalytic Bias in Enzymatic Metal Cofactor-Based Oxidation-Reduction Catalysis

Catalytic bias refers to the relative rate preference of a catalyst for either the forward or reverse direction. In enzymatic metal cofactor-based oxidation-reduction catalysis, the tuning of catalytic bias plays an underlying role in controlling rates of reactivity. For this, enzymes have evolved complex active sites that can exist in multiple oxidation states with differing reduction potentials in order to achieve challenging multi-step, oxidation-reduction reactions. Conceivably, the relative stability of the intermediates that contribute to determining the rate-limiting step of the catalytic cycle could impose catalytic bias, although mechanisms for this concept are just beginning to be realized. As one example, recent work on Clostridium pasteurianum [FeFe]-hydrogenases which catalyze reversible hydrogen oxidation have shown that the differential stabilization/destabilization of active site oxidation states through either static or dynamic protein interactions can preferentially promote either the hydrogen oxidation or proton reduction direction of the reaction. This revealed how an enzymatic cofactor can impose bias in oxidation-reduction catalysis through various tuning mechanisms by protein scaffold interactions. The hypothesis based on achieving catalytic bias through the modulation of cofactor oxidation states critical for the reaction cycle can be extended more generally to other cofactor-based oxidation-reductions catalysts. The current understanding of catalytic bias has significant implications for the design of synthetic catalysts used in industrial settings, as well as providing a greater fundamental understanding of the factors that control metabolic processes in all life.

catalysis↗
DOE OSTI2022

Better together: Protein partnerships for lineage-specific oil accumulation

Plant-derived oils are a major agricultural product that exist in both ubiquitous forms such as common vegetable oils and in specialized forms such as castor oil and coconut oil. These specialized oils are the result of lineage-specific metabolic pathways that create oils rich in unusual fatty acids. Considerable progress has been made toward understanding the enzymes that mediate fatty acid biosynthesis, triacylglycerol assembly, and oil storage. However, efforts to translate this knowledge into renewable bioproducts via engineered oil-producing plants and algae have had limited success. Here, we review recent evidence that protein–protein interactions in each of the three major phases of oil formation appear to have profound effects on specialized oil accumulation. We suggest that furthering our knowledge of the noncatalytic attributes of enzymes and other proteins involved in oil formation will be a critical step toward creating renewable bioproducts derived from high performing, engineered oilseeds.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Lectin Receptor-like Kinase Signaling during Engineered Ectomycorrhiza Colonization

Mutualistic association can improve a plant’s health and productivity. G-type lectin receptor-like kinase (PtLecRLK1) is a susceptibility factor in Populus trichocarpa that permits root colonization by a beneficial fungus, Laccaria bicolor. Engineering PtLecRLK1 also permits L. bicolor root colonization in non-host plants similar to Populus trichocarpa. The intracellular signaling reprogramed by PtLecRLK1 upon recognition of L. bicolor to allow for the development and maintenance of symbiosis is yet to be determined. In this study, phosphoproteomics was utilized to identify phosphorylation-based relevant signaling pathways associated with PtLecRLK1 recognition of L. bicolor in transgenic switchgrass roots. Our finding shows that PtLecRLK1 in transgenic plants modifies the chitin-triggered plant defense and MAPK signaling along with a significant adjustment in phytohormone signaling, ROS balance, endocytosis, cytoskeleton movement, and proteasomal degradation in order to facilitate the establishment and maintenance of L. bicolor colonization. Moreover, protein–protein interaction data implicate a cGMP-dependent protein kinase as a potential substrate of PtLecRLK1.

ectomycorrhiza colonization↗
NASA NTRS2004

Environmental impacts on the developing CNS: CD15, NCAM-L1, and GFAP expression in rat neonates exposed to hypergravity

We have previously reported that the developing rat cerebellum is affected by hypergravity exposure. The effect is observed during a period of both granule and glial cell proliferation and neuronal migration in the cerebellum and coincides with changes in thyroid hormone levels. The present study begins to address the molecular mechanisms involved in the cerebellar response to hypergravity. Specifically, the study focuses on the expression of cerebellar proteins that are known to be directly involved in cell-cell interactions [protein expressing 3-fucosyl-N-acetyl-lactosamine antigen (CD15), neuronal cell adhesion molecule (NCAM-L1)] and those that affect cell-cell interactions indirectly [glial fibrillary acidic protein (GFAP)] in rat neonates exposed to centrifuge-produced hypergravity. Cerebellar mass and protein expression in rat neonates exposed to hypergravity (1.5 G) from gestational day (G) 11 to postnatal day (P) 30 were compared at one of six time points between P6 and P30 against rat neonates developing under normal gravity. Proteins were analyzed by quantitative western blots of cerebellar homogenates prepared from male or female neonates. Cerebellar size was most clearly reduced in male neonates on P6 and in female neonates on P9, with a significant gender difference; differences in cerebellar mass remained significant even when change in total body mass was factored in. Densitometric analysis of western blots revealed both quantitative and temporal changes in the expression of selected cerebellar proteins that coincided with changes in cerebellar mass and were gender-specific. In fact, our data indicated certain significant differences even between male and female control animals. A maximal decrease in expression of CD15 was observed in HG females on P9, coinciding with maximal change in their cerebellar mass. A shift in the time-course of NCAM-L1 expression resulted in a significant increase in NCAM-L1 in HG males on P18, an isolated time at which cerebellar mass does not significantly differ between HG and SC neonates. A maximal decrease in expression of GFAP was observed in HG males on P6, coinciding with maximal change in their cerebellar mass. Altered expression of cerebellar proteins is likely to affect a number of developmental processes and contribute to the structural and functional alterations seen in the CNS developing under altered gravity. Our data suggest that both cerebellar development and its response to gravitational manipulations differ in males and females. c2004 COSPAR. Published by Elsevier Ltd. All rights reserved.

NASA Program Fundamental Space Biology↗
DOE OSTI2022

Kinetic frustration by limited bond availability controls the LAT protein condensation phase transition on membranes

LAT is a membrane-linked scaffold protein that undergoes a phase transition to form a two-dimensional protein condensate on the membrane during T cell activation. Governed by tyrosine phosphorylation, LAT recruits various proteins that ultimately enable condensation through a percolation network of discrete and selective protein-protein interactions. Here, we describe detailed kinetic measurements of the phase transition, along with coarse-grained model simulations, that reveal that LAT condensation is kinetically frustrated by the availability of bonds to form the network. Unlike typical miscibility transitions in which compact domains may coexist at equilibrium, the LAT condensates are dynamically arrested in extended states, kinetically trapped out of equilibrium. Modeling identifies the structural basis for this kinetic arrest as the formation of spindle arrangements, favored by limited multivalent binding interactions along the flexible, intrinsically disordered LAT protein. These results reveal how local factors controlling the kinetics of LAT condensation enable formation of different, stable condensates, which may ultimately coexist within the cell.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
NASA NTRS2001

Palmitoylation of caveolin-1 in endothelial cells is post-translational but irreversible

Caveolin-1 is a palmitoylated protein involved in assembly of signaling molecules in plasma membrane subdomains termed caveolae and in intracellular cholesterol transport. Three cysteine residues in the C terminus of caveolin-1 are subject to palmitoylation, which is not necessary for caveolar targeting of caveolin-1. Protein palmitoylation is a post-translational and reversible modification that may be regulated and that in turn may regulate conformation, membrane association, protein-protein interactions, and intracellular localization of the target protein. We have undertaken a detailed analysis of [(3)H]palmitate incorporation into caveolin-1 in aortic endothelial cells. The linkage of palmitate to caveolin-1 was hydroxylamine-sensitive and thus presumably a thioester bond. However, contrary to expectations, palmitate incorporation was blocked completely by the protein synthesis inhibitors cycloheximide and puromycin. In parallel experiments to show specificity, palmitoylation of aortic endothelial cell-specific nitric-oxide synthase was unaffected by these reagents. Inhibitors of protein trafficking, brefeldin A and monensin, blocked caveolin-1 palmitoylation, indicating that the modification was not cotranslational but rather required caveolin-1 transport from the endoplasmic reticulum and Golgi to the plasma membrane. In addition, immunophilin chaperones that form complexes with caveolin-1, i.e. FK506-binding protein 52, cyclophilin A, and cyclophilin 40, were not necessary for caveolin-1 palmitoylation because agents that bind immunophilins did not inhibit palmitoylation. Pulse-chase experiments showed that caveolin-1 palmitoylation is essentially irreversible because the release of [(3)H]palmitate was not significant even after 24 h. These results show that [(3)H]palmitate incorporation is limited to newly synthesized caveolin-1, not because incorporation only occurs during synthesis but because the continuous presence of palmitate on caveolin-1 prevents subsequent repalmitoylation.

Non-NASA Center↗
DOE OSTI2022

Novel interaction interfaces mediate the interaction between the NEIL1 DNA glycosylase and mitochondrial transcription factor A

The maintenance of human mitochondrial DNA (mtDNA) is critical for proper cellular function as damage to mtDNA, if left unrepaired, can lead to a diverse array of pathologies. Of the pathways identified to participate in DNA repair within the mitochondria, base excision repair (BER) is the most extensively studied. Protein-protein interactions drive the step-by-step coordination required for the successful completion of this pathway and are important for crosstalk with other mitochondrial factors involved in genome maintenance. Human NEIL1 is one of seven DNA glycosylases that initiates BER in both the nuclear and mitochondrial compartments. In the current work, we scrutinized the interaction between NEIL1 and mitochondrial transcription factor A (TFAM), a protein that is essential for various aspects of mtDNA metabolism. We note, for the first time, that both the N- and C- terminal domains of NEIL1 interact with TFAM revealing a unique NEIL1 protein-binding interface. The interaction between the two proteins, as observed biochemically, appears to be transient and is most apparent at concentrations of low salt. The presence of DNA (or RNA) also positively influences the interaction between the two proteins, and molar mass estimates indicate that duplex DNA is required for complex formation at higher salt concentrations. Hydrogen deuterium exchange mass spectrometry data reveal that both proteins exchange less deuterium upon DNA binding, indicative of an interaction, and the addition of NEIL1 to the TFAM-DNA complex alters the interaction landscape. The transcriptional activity of TFAM appears to be independent of NEIL1 expression under normal cellular conditions, however, in the presence of DNA damage, we observe a significant reduction in the mRNA expression of TFAM-transcribed mitochondrial genes in the absence of NEIL1. Overall, our data indicate that the interaction between NEIL1 and TFAM can be modulated by local environment such as salt concentrations, protein availability, the presence of nucleic acids, as well as the presence of DNA damage.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

BIPSPI+: Mining Type-Specific Datasets of Protein Complexes to Improve Protein Binding Site Prediction

Computational approaches for predicting protein-protein interfaces are extremely useful for understanding and modelling the quaternary structure of protein assemblies. In particular, partner-specific binding site prediction methods allow delineating the specific residues that compose the interface of protein complexes. In recent years, new machine learning and other algorithmic approaches have been proposed to solve this problem. However, little effort has been made in finding better training datasets to improve the performance of these methods. With the aim of vindicating the importance of the training set compilation procedure, in this work we present BIPSPI+, a new version of our original server trained on carefully curated datasets that outperforms our original predictor. We show how prediction performance can be improved by selecting specific datasets that better describe particular types of protein interactions and interfaces (e.g. homo/hetero). In addition, our upgraded web server offers a new set of functionalities such as the sequence-structure prediction mode, hetero- or homo-complex specialization and the guided docking tool that allows to compute 3D quaternary structure poses using the predicted interfaces. BIPSPI+ is freely available at https://bipspi.cnb.csic.es.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

High-throughput small-angle X-ray scattering reveals effective structure factor transitions linked to high-concentration antibody viscosity

High-concentration monoclonal antibody (mAb) formulations are often constrained by elevated viscosity, largely driven by protein–protein interactions, which complicates manufacturing and limits subcutaneous delivery. Early viscosity risk assessment is essential during discovery, yet traditional measurements require large sample volumes, and lack high-throughput capability. Here, we develop a high-throughput small-angle X-ray scattering (SAXS) protocol to detect mAb self-association at dilute concentrations, enabling early predictive insights into high-concentration viscosity. Synchrotron SAXS measurements were conducted for 21 mAbs formulated in a histidine buffer at pH 6.0. An initial subset of 10 mAbs analyzed across 1–150 mg/mL revealed that effective structure factor transitions in the low-q region, indicative of interparticle interactions, consistently emerged below 25 mg/mL. Subsequently, 11 additional mAbs were analyzed at 1–25 mg/mL using automated liquid handling and flow cells to enable high-throughput screening. High-viscosity mAbs exhibited detectable low-q upturns at concentrations ≤10 mg/mL, whereas low-viscosity mAbs showed downturns. A classification criterion based on effective structure factor transitions accurately classified all high- and low-viscosity mAbs at 150 mg/mL, offering a scalable, sample-efficient alternative to conventional methods. These results extend recent findings on the concentration-dependent sensitivity of SAXS to short-range attractions, demonstrating that they can emerge at lower concentrations than previously reported. This study presents the most comprehensive and diverse SAXS dataset for mAbs reported to date within a single formulation, providing a valuable resource for developing and validating coarse-grained models that can more accurately capture intermolecular interactions governing high-concentration solution behavior, thereby enabling rational antibody engineering and improved developability.

36 MATERIALS SCIENCE↗
DOE OSTI2024

Leveraging Artificial Intelligence to Expedite Antibody Design and Enhance Antibody–Antigen Interactions

This perspective sheds light on the transformative impact of recent computational advancements in the field of protein therapeutics, with a particular focus on the design and development of antibodies. Cutting-edge computational methods have revolutionized our understanding of protein–protein interactions (PPIs), enhancing the efficacy of protein therapeutics in preclinical and clinical settings. Central to these advancements is the application of machine learning and deep learning, which offers unprecedented insights into the intricate mechanisms of PPIs and facilitates precise control over protein functions. Despite these advancements, the complex structural nuances of antibodies pose ongoing challenges in their design and optimization. Our review provides a comprehensive exploration of the latest deep learning approaches, including language models and diffusion techniques, and their role in surmounting these challenges. We also present a critical analysis of these methods, offering insights to drive further progress in this rapidly evolving field. The paper includes practical recommendations for the application of these computational techniques, supplemented with independent benchmark studies. These studies focus on key performance metrics such as accuracy and the ease of program execution, providing a valuable resource for researchers engaged in antibody design and development. Through this detailed perspective, we aim to contribute to the advancement of antibody design, equipping researchers with the tools and knowledge to navigate the complexities of this field.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2022

Resolving the fine structure in the energy landscapes of repeat proteins

Ankyrin (ANK) repeat proteins are coded by tandem occurrences of patterns with around 33 amino acids. They often mediate protein–protein interactions in a diversity of biological systems. These proteins have an elongated non-globular shape and often display complex folding mechanisms. This work investigates the energy landscape of representative proteins of this class made up of 3, 4 and 6 ANK repeats using the energy-landscape visualisation method (ELViM). By combining biased and unbiased coarse-grained molecular dynamics AWSEM simulations that sample conformations along the folding trajectories with the ELViM structure-based phase space, one finds a three-dimensional representation of the globally funnelled energy surface. In this representation, it is possible to delineate distinct folding pathways. We show that ELViMs can project, in a natural way, the intricacies of the highly dimensional energy landscapes encoded by the highly symmetric ankyrin repeat proteins into useful low-dimensional representations. These projections can discriminate between multiplicities of specific parallel folding mechanisms that otherwise can be hidden in oversimplified depictions.

Murilo N. Sanches↗
NASA NTRS1999

ARG1 (altered response to gravity) encodes a DnaJ-like protein that potentially interacts with the cytoskeleton

Gravitropism allows plant organs to direct their growth at a specific angle from the gravity vector, promoting upward growth for shoots and downward growth for roots. Little is known about the mechanisms underlying gravitropic signal transduction. We found that mutations in the ARG1 locus of Arabidopsis thaliana alter root and hypocotyl gravitropism without affecting phototropism, root growth responses to phytohormones or inhibitors of auxin transport, or starch accumulation. The positional cloning of ARG1 revealed a DnaJ-like protein containing a coiled-coil region homologous to coiled coils found in cytoskeleton-interacting proteins. These data suggest that ARG1 participates in a gravity-signaling process involving the cytoskeleton. A combination of Northern blot studies and analysis of ARG1-GUS fusion-reporter expression in transgenic plants demonstrated that ARG1 is expressed in all organs. Ubiquitous ARG1 expression in Arabidopsis and the identification of an ortholog in Caenorhabditis elegans suggest that ARG1 is involved in other essential processes.

Non-NASA Center↗
DOE OSTI2026

Artificial intelligence methods for protein structure and interaction prediction: Recent advances and challenges

Recent advances in artificial intelligence have introduced novel methods for high-accuracy prediction of protein tertiary structures, protein complex structures, and interactions between proteins and other biomolecules, such as small molecules and nucleic acids. Such advancements are accelerating biomedical research and the development of new protein design and bioengineering methods among many other important biotechnology applications. Here, in this review, we outline the recent advances in protein-centric biomolecular structure and interaction prediction, highlight some major challenges in the field, and discuss potential directions to address them.

Morehead, Alex [Lawrence Berkeley National Laborat↗
DOE OSTI2024

Structure of HIV-1 RRE stem-loop II identifies two conformational states of the high-affinity Rev binding site

During HIV infection, specific RNA-protein interaction between the Rev response element (RRE) and viral Rev protein is required for nuclear export of intron-containing viral mRNA transcripts. Rev initially binds the high-affinity site in stem-loop II, which promotes oligomerization of additional Rev proteins on RRE. Here, we present the crystal structure of RRE stem-loop II in distinct closed and open conformations. The high-affinity Rev-binding site is located within the three-way junction rather than the predicted stem IIB. The closed and open conformers differ in their non-canonical interactions within the three-way junction, and only the open conformation has the widened major groove conducive to initial Rev interaction. Rev binding assays show that RRE stem-loop II has high- and low-affinity binding sites, each of which binds a Rev dimer. We propose a binding model, wherein Rev-binding sites on RRE are sequentially created through structural rearrangements induced by Rev-RRE interactions.

60 APPLIED LIFE SCIENCES↗