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The Drosophila G protein‐coupled receptor, Methuselah, exhibits a promiscuous response to peptides
Author(s) -
Ja William W.,
Carvalho Gil B.,
Madrigal Marisol,
Roberts Richard W.,
Benzer Seymour
Publication year - 2009
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.221
Subject(s) - g protein coupled receptor , drosophila melanogaster , peptide , biology , receptor , homology modeling , computational biology , promiscuity , agonist , alanine scanning , microbiology and biotechnology , mutant , genetics , biochemistry , enzyme , gene , mutagenesis , ecology
Methuselah (Mth) is a G protein‐coupled receptor (GPCR) associated with longevity in Drosophila melanogaster . Previously, Stunted (Sun) was identified as a peptide agonist of Mth. Here, we identify two additional activators of Mth signaling: Drosophila Sex Peptide (SP) and a novel peptide (Serendipitous Peptide Activator of Mth, SPAM). Minimal functional sequences and key residues were identified from Sun and SPAM by studying truncation and alanine‐scanning mutations. These peptide agonists share little sequence homology and illustrate the promiscuity of Mth for activation. mth mutants exhibit no defects in behaviors controlled by SP, casting doubt on the biological significance of Mth activation by any of these agonists, and illustrating the difficulty in applying in vitro studies to their relevance in vivo . Future studies of Mth ligands will help further our understanding of the functional interaction of agonists and GPCRs.