2026-04-13T01:52:35Zhttps://recercat.cat/oai/request
oai:recercat.cat:2072/4602082024-11-04T02:19:44Zcom_2072_98col_2072_378192
RECERCAT author Wang, Li-Ying author Ravi, Vidhya M. author Leblanc, Gérard author Padrós, Esteve author Cladera i Cerdà, Josep author Perálvarez-Marín, Alex 2024-11-04T02:19:44Z 2024-11-04T02:19:44Z 2016 http://hdl.handle.net/2072/460208 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. open access Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. https://creativecommons.org/licenses/by/4.0/ Helical unwinding and side-chain unlocking unravel the outward open conformation of the melibiose transporter Article