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NASA NTRS · 20040112354

Structural models of the MscL gating mechanism

Sukharev, S.·Durell, S. R.·Guy, H. R.
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Abstract

Three-dimensional structural models of the mechanosensitive channel of large conductance, MscL, from the bacteria Mycobacterium tuberculosis and Escherichia coli were developed for closed, intermediate, and open conformations. The modeling began with the crystal structure of M. tuberculosis MscL, a homopentamer with two transmembrane alpha-helices, M1 and M2, per subunit. The first 12 N-terminal residues, not resolved in the crystal structure, were modeled as an amphipathic alpha-helix, called S1. A bundle of five parallel S1 helices are postulated to form a cytoplasmic gate. As membrane tension induces expansion, the tilts of M1 and M2 are postulated to increase as they move away from the axis of the pore. Substantial expansion is postulated to occur before the increased stress in the S1 to M1 linkers pulls the S1 bundle apart. During the opening transition, the S1 helices and C-terminus amphipathic alpha-helices, S3, are postulated to dock parallel to the membrane surface on the perimeter of the complex. The proposed gating mechanism reveals critical spatial relationships between the expandable transmembrane barrel formed by M1 and M2, the gate formed by S1 helices, and "strings" that link S1s to M1s. These models are consistent with numerous experimental results and modeling criteria.

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NASA Discipline Cell BiologyNon-NASA CenterIon Channels/chemistry/metabolismIon Channel GatingMycobacterium tuberculosis/chemistryEscherichia coli ProteinsEscherichia coli/chemistryModels, MolecularProtein Structure, SecondaryMolecular Sequence DataSupport, U.S. Gov't, Non-P.H.SConserved SequenceAmino Acid SequenceGenome, BacterialKineticsCrystallography, X-RaySupport, U.S. Gov't, P.H.S

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Sukharev, S., Durell, S. R., Guy, H. R.. 2001-08-01. Structural models of the MscL gating mechanism. https://ntrs.nasa.gov/citations/20040112354

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