| Autor: |
Chandra M Khantwal, Sherwin J Abraham, Wei Han, Tao Jiang, Tanmay S Chavan, Ricky C Cheng, Shelley M Elvington, Corey W Liu, Irimpan I Mathews, Richard A Stein, Hassane S Mchaourab, Emad Tajkhorshid, Merritt Maduke |
| Jazyk: |
angličtina |
| Rok vydání: |
2016 |
| Předmět: |
|
| Zdroj: |
eLife, Vol 5 (2016) |
| Druh dokumentu: |
article |
| ISSN: |
2050-084X |
| DOI: |
10.7554/eLife.11189 |
| Popis: |
CLC secondary active transporters exchange Cl- for H+. Crystal structures have suggested that the conformational change from occluded to outward-facing states is unusually simple, involving only the rotation of a conserved glutamate (Gluex) upon its protonation. Using 19F NMR, we show that as [H+] is increased to protonate Gluex and enrich the outward-facing state, a residue ~20 Å away from Gluex, near the subunit interface, moves from buried to solvent-exposed. Consistent with functional relevance of this motion, constriction via inter-subunit cross-linking reduces transport. Molecular dynamics simulations indicate that the cross-link dampens extracellular gate-opening motions. In support of this model, mutations that decrease steric contact between Helix N (part of the extracellular gate) and Helix P (at the subunit interface) remove the inhibitory effect of the cross-link. Together, these results demonstrate the formation of a previously uncharacterized 'outward-facing open' state, and highlight the relevance of global structural changes in CLC function. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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