Exploration of conformational changes in lactose permease upon sugar binding and proton transfer through coarse-grained simulations.
Proteins
; 85(10): 1856-1865, 2017 Oct.
Article
en En
| MEDLINE
| ID: mdl-28639287
ABSTRACT
Escherichia coli lactose permease (LacY) actively transports lactose and other galactosides across cell membranes through lactose/H+ symport process. Lactose/H+ symport is a highly complex process that involves sugar translocation, H+ transfer, and large-scale protein conformational changes. The complete picture of lactose/H+ symport is largely unclear due to the complexity and multiscale nature of the process. In this work, we develop the force field for sugar molecules compatible with PACE, a hybrid and coarse-grained force field that couples the united-atom protein models with the coarse-grained MARTINI water/lipid. After validation, we implement the new force field to investigate the binding of a ß-d-galactopyranosyl-1-thio- ß-d-galactopyranoside (TDG) molecule to a wild-type LacY. Results show that the local interactions between TDG and LacY at the binding pocket are consistent with the X-ray experiment. Transitions from inward-facing to outward-facing conformations upon TDG binding and protonation of Glu269 have been achieved from â¼5.5 µs simulations. Both the opening of the periplasmic side and closure of the cytoplasmic side of LacY are consistent with double electron-electron resonance and thiol cross-linking experiments. Our analysis suggests that the conformational changes of LacY are a cumulative consequence of interdomain H-bonds breaking at the periplasmic side, interdomain salt-bridge formation at the cytoplasmic side, and the TDG orientational changes during the transition.
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Texto completo:
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Bases de datos:
MEDLINE
Asunto principal:
Proteínas de Transporte de Membrana
/
Conformación Proteica
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Simportadores
/
Lactosa
Idioma:
En
Revista:
Proteins
Asunto de la revista:
BIOQUIMICA
Año:
2017
Tipo del documento:
Article