Dataset Information

Helical unwinding and side-chain unlocking unravel the outward open conformation of the melibiose transporter.

ABSTRACT: Molecular dynamics simulations have been used to study the alternate access mechanism of the melibiose transporter from Escherichia coli. Starting from the outward-facing partially occluded form, 2 out of 12 simulations produced an outward full open form and one partially open, whereas the rest yielded fully or partially occluded forms. The shape of the outward-open form resembles other outward-open conformations of secondary transporters. During the transporter opening, conformational changes in some loops are followed by changes in the periplasm region of transmembrane helix 7. Helical curvature relaxation and unlocking of hydrophobic and ionic locks promote the outward opening of the transporter making accessible the substrate binding site. In particular, FRET studies on mutants of conserved aromatic residues of extracellular loop 4 showed lack of substrate binding, emphasizing the importance of this loop for making crucial interactions that control the opening of the periplasmic side. This study indicates that the alternate access mechanism for the melibiose transporter fits better into a flexible gating mechanism rather than the archetypical helical rigid-body rocker-switch mechanism.

SUBMITTER: Wang LY

PROVIDER: S-EPMC5034317 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Helical unwinding and side-chain unlocking unravel the outward open conformation of the melibiose transporter.

Wang Li-Ying LY Ravi Vidhya M VM Leblanc Gérard G Padrós Esteve E Cladera Josep J Perálvarez-Marín Alex A

Scientific reports 20160923

Molecular dynamics simulations have been used to study the alternate access mechanism of the melibiose transporter from Escherichia coli. Starting from the outward-facing partially occluded form, 2 out of 12 simulations produced an outward full open form and one partially open, whereas the rest yielded fully or partially occluded forms. The shape of the outward-open form resembles other outward-open conformations of secondary transporters. During the transporter opening, conformational changes i ...[more]

PMID: 27658476

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Dataset Information

Helical unwinding and side-chain unlocking unravel the outward open conformation of the melibiose transporter.

Publications

Helical unwinding and side-chain unlocking unravel the outward open conformation of the melibiose transporter.

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