Linked Life Data

8930157

Source:http://linkedlifedata.com/resource/pubmed/id/8930157

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1996-12-24
pubmed:abstractText
The affinity and specificity of the binding interaction between ligands and their receptors are key for appropriate hormonal regulation of target tissues. However, it is now apparent that vasoactive intestinal polypeptide (VIP) binds to the rat secretin receptor with similar affinity to that for its natural ligand, secretin (Holtmann et al., 1995). In this report, we establish that this is not a characteristic of the human secretin receptor, and use rat-human secretin receptor chimeras, site mutants and truncated receptor constructs to establish the molecular basis for this unusual binding interaction. Of note, isolated N-terminal domains of the rat secretin and the VIP receptors are capable of high affinity binding of VIP. In the recently recognized secretin family of receptors, this domain has six conserved cysteine residues and disulfide bonds that are likely important to achieve the complex conformation critical for this binding. A single acidic residue (Asp98) present in the rat secretin receptor appears to be critical, because a site-mutant changing this to the polar, but uncharged residue present in that position in the human receptor (Asn) eliminates the high affinity binding of VIP. Of interest, a previously identified critical basic residue in VIP (Lys15) provides a candidate for charge-pairing with this residue, potentially aligning the peptide ligand in a nonproductive orientation within this receptor.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
555-60
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Molecular basis and species specificity of high affinity binding of vasoactive intestinal polypeptide by the rat secretin receptor.
pubmed:affiliation
Center for Basic Research in Digestive Diseases, Mayo Clinic and Foundation, Rochester, Minnesota, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't