Revealing an outward-facing open conformational state in a CLC Cl <sup>–</sup>/H <sup>+</sup> exchange transporter [electronic resource]

Saved in:
Bibliographic Details
Online Access: Online Access
Format: Government Document Electronic eBook
Language:English
Published: Washington, D.C. : Oak Ridge, Tenn. : United States. Department of Energy. Office of Science ; distributed by the Office of Scientific and Technical Information, U.S. Department of Energy, 2016.
Subjects:

MARC

LEADER 00000nam a22000003u 4500
001 b8795663
003 CoU
005 20160527234919.3
006 m o d f
007 cr |||||||||||
008 160906e20160122||| o| f0|||||eng|d
035 |a (TOE)ost1254484 
035 |a (TOE)1254484 
040 |a TOE  |c TOE 
049 |a GDWR 
072 7 |a 37  |2 edbsc 
086 0 |a E 1.99:1254484 
086 0 |a E 1.99:1254484 
245 0 0 |a Revealing an outward-facing open conformational state in a CLC Cl <sup>–</sup>/H <sup>+</sup> exchange transporter  |h [electronic resource] 
260 |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. 
300 |a Article No. e11189 :  |b digital, PDF file. 
336 |a text  |b txt  |2 rdacontent. 
337 |a computer  |b c  |2 rdamedia. 
338 |a online resource  |b cr  |2 rdacarrier. 
500 |a Published through SciTech Connect. 
500 |a 01/22/2016. 
500 |a eLife 5 ISSN 2050-084X AM. 
500 |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. 
500 |a Stanford Univ. School of Medicine, Stanford, CA (United States) 
520 3 |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> 
536 |b AC02-76SF00515. 
536 |b MCA06N060. 
650 7 |a Inorganic, Organic, Physical, And Analytical Chemistry.  |2 edbsc. 
710 1 |a United States.  |b Department of Energy.  |b Office of Science.  |4 spn. 
710 1 |a United States.  |b Department of Energy.  |b Office of Scientific and Technical Information.  |4 dst. 
856 4 0 |u http://www.osti.gov/scitech/biblio/1254484  |z Online Access 
907 |a .b87956639  |b 03-08-23  |c 09-08-16 
998 |a web  |b 09-08-16  |c f  |d m   |e p  |f eng  |g    |h 0  |i 1 
956 |a Information bridge 
999 f f |i 40ac9f63-bb7c-5173-9888-679447a57d16  |s 4afca14c-1af5-5f8a-aabc-50fbd2d42dcc 
952 f f |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