2024-03-29T06:48:30Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/629862016-02-17T11:53:21Zcom_10261_133com_10261_1col_10261_386
2012-12-14T13:01:18Z
urn:hdl:10261/62986
Interactions between loop 5 and β-strand β6′ are involved in α7 nicotinic acetylcholine receptors channel gating
Criado, Manuel
Mulet Soler, José
Castillo-Paterna, Mar
Aldea, Marcos
Sala, Salvador
Sala, Francisco
Binding of agonists to nicotinic acetylcholine receptors (nAChR) is coupled to channel opening through local rearrangements of different domains of the protein. Recent structural data suggest that two of these regions could be the loop 5 (L5) and the β-strand β6′, both forming the inner part of the N-terminal domain. Amino acids in these domains were mutated in α7 nAChRs, and expression levels and functional responses of mutant receptors were measured. Mutations located at the putative apex of L5, Asp97 and Glu98, and also at Phe100, gave receptors with smaller currents, showing qualitative differences with respect to muscle nAChRs. In contrast, mutations in the β-strand β6′ (at Phe124 and Lys125) showed increased functional responses. Mutations affected equally the responses to acetylcholine and dimethylphenylpiperazinium, except in Phe100 where the latter was sevenfold less effective than in wild-type. Currents in mutants decayed with almost the same kinetics, ruling out large effects on desensitization. Analysis of double mutants demonstrated a functional coupling among the three electrically charged amino acids Asp97, Glu98, and Lys125, and also between Phe100 and Phe124. The results are compatible with the involvement of functional interactions between L5 and β-strand β6′ during nAChR activation. © 2007 The Authors.
2012-12-14T13:01:18Z
2012-12-14T13:01:18Z
2008
2012-12-14T13:01:18Z
artículo
Journal of Neurochemistry 104(3): 719-730 (2008)
http://hdl.handle.net/10261/62986
10.1111/j.1471-4159.2007.05010.x
eng
closedAccess
Blackwell Publishing