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|a (TOE)ost1254484
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|a E 1.99:1254484
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|a E 1.99:1254484
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|a Revealing an outward-facing open conformational state in a CLC Cl <sup>–</sup>/H <sup>+</sup> exchange transporter
|h [electronic resource]
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|a Washington, D.C. :
|b United States. Department of Energy. Office of Science ;
|a Oak Ridge, Tenn. :
|b distributed by the Office of Scientific and Technical Information, U.S. Department of Energy,
|c 2016.
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|a Article No. e11189 :
|b digital, PDF file.
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|a text
|b txt
|2 rdacontent.
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|a computer
|b c
|2 rdamedia.
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|a online resource
|b cr
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|a Published through SciTech Connect.
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|a 01/22/2016.
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|a eLife 5 ISSN 2050-084X AM.
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|a Han, Wei; Jiang, Tao; Liu, Corey W.; Tajkhorshid, Emad; Mathews, Irimpan I.; Stein, Richard A.; Mchaourab, Hassane S.; Khantwal, Chandra M.; Abraham, Sherwin J.; Chavan, Tanmay S.; Cheng, Ricky C.; Elvington, Shelley M.; Maduke, Merritt.
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|a Stanford Univ. School of Medicine, Stanford, CA (United States)
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|a <p>CLC secondary active transporters exchange Cl<sup>-</sup>for H<sup>+</sup>. 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 (Glu<sub>ex</sub>) upon its protonation. Using<sup>19</sup>F NMR, we show that as [H<sup>+</sup>] is increased to protonate Glu<sub>ex</sub>and enrich the outward-facing state, a residue ̃20 Å away from Glu<sub>ex</sub>, 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. In conclusion, 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.</p>
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|b AC02-76SF00515.
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|b MCA06N060.
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|a Inorganic, Organic, Physical, And Analytical Chemistry.
|2 edbsc.
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|a United States.
|b Department of Energy.
|b Office of Science.
|4 spn.
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|a United States.
|b Department of Energy.
|b Office of Scientific and Technical Information.
|4 dst.
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|u http://www.osti.gov/scitech/biblio/1254484
|z Online Access
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|a .b87956639
|b 03-08-23
|c 09-08-16
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|b 09-08-16
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|p Can circulate
|a University of Colorado Boulder
|b Online
|c Online
|d Online
|e E 1.99:1254484
|h Superintendent of Documents classification
|i web
|n 1
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