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Acetylcholine receptor αM3 domain reveals a spring‐tilted motion during channel activation: structural and functional differences between Torpedo and muscle‐type
Author(s) -
OteroCruz Jose David,
LasaldeDominicci Jose Antonio
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.lb60
Subject(s) - torpedo , nicotinic acetylcholine receptor , acetylcholine receptor , chemistry , ion channel , biophysics , acetylcholine , helix (gastropod) , nicotinic agonist , neuromuscular junction , crystallography , receptor , biochemistry , neuroscience , biology , endocrinology , ecology , snail
It has been proposed that lipid‐exposed domains play a significant role in the conformational transitions of the nicotinic acetylcholine receptor (nAChR), which mediates the transmission of nerve signals across synapses. The role of the αM3 domain in ion channel function of the muscle‐type nAChR was examined using tryptophan‐scanning mutagenesis. The tryptophan periodicity profiles suggest two different helical structures; a thinner‐elongated helix for the closed state and a thicker‐shrunken helix for the open‐channel state. The existence of two different helical structures is plausible with a spring‐tilted motion by the αM3 domain during acetylcholine‐induced activation of the nAChR. The present study also provides compelling evidence about ion channel function and structure differences between the αM3 domains of the muscle‐type and Torpedo californica nAChRs. Our data also suggest that both nAChR species have different space requirements at the ends during closed state, have different amount of internal hydrogen bonds and exhibit functional divergence at the lower half region, from αI286 to αI290 residues, during open‐channel state. The spring‐tilted model also suggests that the lipid‐protein interface of the nAChR could play a key role in the propagation of the conformational wave evoked by agonist activation. Support Contributed By: NIH RO1GM56371 and GM08102‐27 grants awarded to J.A.L.‐D and NIH‐MBRS‐RISE 5R25GM61151 and NSF‐AGEP HRD‐0302696 grants awarded to J.D.O.‐C.