Role of loop 9 on the function of neuronal nicotinic receptors.
We have studied the role of loop 9 in the function of neuronal nicotinic receptors. By systematically mutating the residues in the loop we have determined that the most important amino acids determining the coupling of binding to gating are the ones closer to the transmembrane region. Single mutations at location E173 in homomeric alpha7 receptors destroyed their function by completely abolishing the current while preserving the expression at the membrane. In contrast, heteromeric receptor alpha3beta4 with the same mutations retained some function. We conclude that loop 9 has a different role in the function of homomeric and heteromeric receptors.
Criado
Manuel
M
Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, Sant Joan d'Alacant, 03550-Alicante, Spain.
Castillo
Mar
M
Mulet
José
J
Sala
Francisco
F
Sala
Salvador
S
D000109:Acetylcholine / Q000494:pharmacology; D000409:Alanine / Q000235:genetics; D000818:Animals; D002417:Cattle; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D016296:Mutagenesis / Q000187:drug effects; D050505:Mutant Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000378:metabolism*; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D051381:Rats; D011978:Receptors, Nicotinic / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014982:Xenopus laevis
D050505:Mutant Proteins; D011978:Receptors, Nicotinic; D000109:Acetylcholine; D000409:Alanine