Acetylcholine receptor gating at extracellular transmembrane domain interface: the cys-loop and m2 m3 linker.

Acetylcholine receptor gating at extracellular transmembrane domain interface: the cys-loop and m2 m3 linker. Research Abstract Details 

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Acetylcholine receptor gating at extracellular transmembrane domain interface: the cys-loop and m2 m3 linker. Abstract Text:

Archana Jha,David J Cadugan,Prasad Purohit,Anthony Auerbach,Archana Jha,David J Cadugan,Prasad Purohit,Anthony Auerbach,

Acetylcholine receptor channel gating is a propagated conformational cascade that links changes in structure and function at the transmitter binding sites in the extracellular domain (ECD) with those at a "gate" in the transmembrane domain (TMD). We used Phi-value analysis to probe the relative timing of the gating motions of alpha-subunit residues located near the ECD-TMD interface. Mutation of four of the seven amino acids in the M2-M3 linker (which connects the pore-lining M2 helix with the M3 helix), including three of the four residues in the core of the linker, changed the diliganded gating equilibrium constant (K(eq)) by up to 10,000-fold (P272 > I274 > A270 > G275). The average Phi-value for the whole linker was approximately 0.64. One interpretation of this result is that the gating motions of the M2-M3 linker are approximately synchronous with those of much of M2 ( approximately 0.64), but occur after those of the transmitter binding site region ( approximately 0.93) and loops 2 and 7 ( approximately 0.77). We also examined mutants of six cys-loop residues (V132, T133, H134, F135, P136, and F137). Mutation of V132, H134, and F135 changed K(eq) by 2800-, 10-, and 18-fold, respectively, and with an average Phi-value of 0.74, similar to those of other cys-loop residues. Even though V132 and I274 are close, the energetic coupling between I and V mutants of these positions was small (

Acetylcholine receptor gating at extracellular transmembrane domain interface: the cys-loop and m2 m3 linker. Publishing Authors By Initials

A Jha,DJ Cadugan,P Purohit,A Auerbach,A Jha,DJ Cadugan,P Purohit,A Auerbach,

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Acetylcholine receptor gating at extracellular transmembrane domain interface: the cys-loop and m2 m3 linker. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: The Journal of general physiology

VOLUME: 130

Page Numbers: 547-58

Journal Abbreviation: J. Gen. Physiol.

ISSN: 0022-1295

DAY: 27

MONTH: Dec

YEAR: 2007

Acetylcholine receptor gating at extracellular transmembrane domain interface: the cys-loop and m2 m3 linker. Information

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LANGUAGE: eng

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AFFILIATION: Correspondence to Anthony Auerbach: auerbach@buffalo.edu.

Country: United States

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MEDLINETA: J Gen Physiol

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