Proton Transport Pathway in the ClC Cl−/H+ Antiporter
AUTOR(ES)
Wang, Dong
FONTE
The Biophysical Society
RESUMO
A fundamental question concerning the ClC Cl−/H+ antiporters is the nature of their proton transport (PT) pathway. We addressed this issue by using a novel computational methodology capable of describing the explicit PT dynamics in the ClC-ec1 protein. The main result is that the Glu203 residue delivers a proton from the intracellular solution to the core of ClC-ec1 via a rotation of its side chain and subsequent acid dissociation. After reorientation of the Glu203 side chain, a transient water-mediated PT pathway between Glu203 and Glu148 is established that is able to receive and translocate the proton via Grotthuss shuttling after deprotonation of Glu203. A molecular-dynamics simulation of an explicit hydrated excess proton in this pathway suggests that a negatively charged Glu148 and the central Cl− ion act together to drive H+ to the extracellular side of the membrane. This finding is consistent with the experimental result that Cl− binding to the central site facilitates the proton movement. A calculation of the PT free-energy barrier for the ClC-ec1 E203V mutant also supports the proposal that a dissociable residue is required at this position for efficient delivery of H+ to the protein interior, in agreement with recent experimental results.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2711357Documentos Relacionados
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