Linked Life Data

17286976

Source:http://linkedlifedata.com/resource/pubmed/id/17286976

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-3
pubmed:dateCreated
2007-8-1
pubmed:abstractText
Recently, we cloned many of the bullfrog neuropeptide G protein-coupled receptors (GPCRs), including receptors for vasotocin (VT), mesotocin, gonadotropin-releasing hormone (GnRH), neurotensin, apelin, and metastin. Bullfrog GPCRs usually have high affinity for bullfrog ligands but relatively low affinity for mammalian ligands. Reciprocally, synthetic agonists and antagonists developed based upon mammalian ligands display lower affinity at bullfrog receptors. Studies using chimeric or domain-swapped receptors indicate that the motifs responsible for differential ligand selectivity usually reside within transmembrane domain 6 (TMD6)-extracellular loop 3 (ECL3)-transmembrane domain 7 (TMD7). Triple mutation of mammalian V1aR (Phe(6.51) to Tyr, Ile(6.53) to Thr, and Pro(7.33) to Thr) increases VT affinity but greatly reduces arginine vasopressin affinity. This binding profile is similar to that of bullfrog VT1R. Changing just three amino acids in the bullfrog GnRH receptor-1 (i.e. Ser-Gln-Ser in the ECL3) to those found in the type-I mammalian GnRH receptor (i.e. Ser-Glu-Pro) reverses GnRH selectivity. In conclusion, specific receptor motifs that govern ligand selectivity can be determined by comparative molecular analyses of GPCRs and their ligands. Such analysis provides clues for understanding how GPCRs maintain high affinity to their authentic ligands.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0016-6480
pubmed:author
pubmed:issnType
Print
pubmed:volume
153
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
98-107
pubmed:dateRevised
2007-11-19
pubmed:meshHeading
pubmed:articleTitle
Molecular evolution of neuropeptide receptors with regard to maintaining high affinity to their authentic ligands.
pubmed:affiliation
Graduate School of Medicine, Korea University, Seoul 136-705, Republic of Korea.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't