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Title

Mutants of β-strand β3 and the loop B in the interface between α7 subunits of a homomeric acetylcholine receptor show functional and pharmacological alterations

AuthorsCriado, Manuel CSIC ORCID; Mulet Soler, José; Gerber, Susana; Sala, Salvador; Sala, Francisco
KeywordsAcetylcholine receptor
Channel gating
Loop B
Mutant
Strand beta3
Xenopus oocytes
Issue DateSep-2011
PublisherWiley-Blackwell
CitationJournal of Neurochemistry 118(6): 968-978 (2011)
AbstractActivation of nicotinic acetylcholine receptors (nAChR) requires a global conformational change involving a number of domains of the protein. Structural data from Torpedo nAChR suggest that adjacent subunits might be functionally coupled at the interface between the β-strand β3 and the loop B through a salt bridge between α1Asp152 and γArg78. We have checked this hypothesis in homomeric α7 nAChRs by mutating residues at these (Gly152 and Arg79) and neighboring locations and analyzing the results obtained after expression of single and double mutants in Xenopus oocytes. We found that Arg79 mutants showed a decreased gating function when challenged with different agonists, being the reduction more important for dimethylphenylpiperazinium. EC 50 values in these mutants were also increased up to 30-fold. In contrast, mutating Gly152 only showed significant higher EC 50 values for ACh. However, all Gly153 mutants presented increased gating function and lower EC 50 values with no significant differences among them. When analyzing several mutant cycles it is concluded that Arg79 is functionally coupled to Gly152, but neither to Gly153 nor to Asp157. These data suggest an involvement of the minus side of homomeric α7 nAChRs in their gating function, reinforcing the significance of complementary subunits in the gating of neuronal nAChRs.
Description11 p., 7 figures, 2 tables and references.
Publisher version (URL)http://dx.doi.org/10.1111/j.1471-4159.2011.07381.x
URIhttp://hdl.handle.net/10261/54960
DOI10.1111/j.1471-4159.2011.07381.x
ISSN0022-3042
E-ISSN1471-4159
Appears in Collections:(IN) Artículos

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