Differential surface accessibility of alpha(187-199) in the Torpedo acetylcholine receptor alpha subunits.

Abstract:

:We have probed the surface accessibility of residues alpha187 to alpha199 of the Torpedo acetylcholine receptor with monoclonal antibody 383C, which binds uniquely to these residues. However, 383C binds to only one of the two alpha subunits in the membrane-bound receptor, neither of the two subunits in carbamylcholine-desensitized receptor, and to both alpha subunits in Triton X-100 solubilized receptor. The kinetics of association and dissoci-ation of 383C with the peptide alpha(183-199) compared to those with the membrane-bound receptor suggest that all but a single hydrogen bond of affinity derives from contacts between this peptide and the monoclonal antibody paratope. Inhibition of 383C binding by alpha-bungarotoxin selectively directed to the alpha subunit correlated with the high-affinity d-tubocurarine binding site, along with a lack of inhibition by alpha-bungarotoxin directed to the alpha subunit correlated with the low-affinity d-tubocurarine binding site, suggests that the 383C epitope on the membrane-bound receptor resides on the alpha subunit associated with the high-affinity d-tubocurarine binding site. The results presented here suggest a structural basis for the differences between the two receptor acetylcholine binding sites.

journal_name

J Mol Biol

authors

Fairclough RH,Twaddle GM,Gudipati E,Lin MY,Richman DP

doi

10.1006/jmbi.1998.2001

subject

Has Abstract

pub_date

1998-09-18 00:00:00

pages

317-30

issue

2

eissn

0022-2836

issn

1089-8638

pii

S0022-2836(98)92001-0

journal_volume

282

pub_type

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