Ion permeation through a Cl−-selective channel designed from a CLC Cl−/H+ exchanger Export

@article{citeulike:3969934, abstract = {10.1073/pnas.0804503105 The CLC family of Cl-transporting proteins includes both Cl channels and Cl/H exchange transporters. CLC-ec1, a structurally known bacterial homolog of the transporter subclass, exchanges two Cl ions per proton with strict, obligatory stoichiometry. Point mutations at two residues, Glu and Tyr, are known to impair H movement while preserving Cl transport. In the x-ray crystal structure of CLC-ec1, these residues form putative ” gates” flanking an ion-binding region. In mutants with both of the gate-forming side chains reduced in size, H transport is abolished, and unitary Cl transport rates are greatly increased, well above values expected for transporter mechanisms. Cl transport rates increase as side-chain volume at these positions is decreased. The crystal structure of a doubly ungated mutant shows a narrow conduit traversing the entire protein transmembrane width. These characteristics suggest that Cl flux through uncoupled, ungated CLC-ec1 occurs via a channel-like electrodiffusion mechanism rather than an alternating-exposure conformational cycle that has been rendered proton-independent by the gate mutations.}, author = {Jayaram, Hariharan and Accardi, Alessio and Wu, Fang and Williams, Carole and Miller, Christopher}, citeulike-article-id = {3969934}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0804503105}, citeulike-linkout-1 = {http://www.pnas.org/content/105/32/11194.abstract}, citeulike-linkout-2 = {http://www.pnas.org/content/105/32/11194.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/18678918}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=18678918}, day = {12}, doi = {10.1073/pnas.0804503105}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, keywords = {channel, clc}, month = {August}, number = {32}, pages = {11194--11199}, posted-at = {2009-08-09 08:46:55}, priority = {2}, title = {Ion permeation through a Cl−-selective channel designed from a CLC Cl−/H+ exchanger}, url = {http://dx.doi.org/10.1073/pnas.0804503105}, volume = {105}, year = {2008} }

TY - JOUR ID - citeulike:3969934 L3 - citeulike-article-id:3969934 N2 - 10.1073/pnas.0804503105 The CLC family of Cl-transporting proteins includes both Cl channels and Cl/H exchange transporters. CLC-ec1, a structurally known bacterial homolog of the transporter subclass, exchanges two Cl ions per proton with strict, obligatory stoichiometry. Point mutations at two residues, Glu and Tyr, are known to impair H movement while preserving Cl transport. In the x-ray crystal structure of CLC-ec1, these residues form putative “gates” flanking an ion-binding region. In mutants with both of the gate-forming side chains reduced in size, H transport is abolished, and unitary Cl transport rates are greatly increased, well above values expected for transporter mechanisms. Cl transport rates increase as side-chain volume at these positions is decreased. The crystal structure of a doubly ungated mutant shows a narrow conduit traversing the entire protein transmembrane width. These characteristics suggest that Cl flux through uncoupled, ungated CLC-ec1 occurs via a channel-like electrodiffusion mechanism rather than an alternating-exposure conformational cycle that has been rendered proton-independent by the gate mutations. IS - 32 JF - Proceedings of the National Academy of Sciences SN - 1091-6490 EP - 11199 TI - Ion permeation through a Cl−-selective channel designed from a CLC Cl−/H+ exchanger VL - 105 SP - 11194 KW - channel KW - clc AU - Jayaram, Hariharan AU - Accardi, Alessio AU - Wu, Fang AU - Williams, Carole AU - Miller, Christopher PY - 2008/08/12/ UR - http://dx.doi.org/10.1073/pnas.0804503105 ER -