Linked Life Data

19459609

Source:http://linkedlifedata.com/resource/pubmed/id/19459609

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
2009-6-9
pubmed:abstractText
The C-terminal segment of the insulin receptor (IR) alpha-chain plays a critical role in insulin binding. This 16-residue peptide together with the central beta-sheet of the receptor L1 domain forms one of the insulin binding surfaces of the IR monomer. Here we use isothermal titration calorimetry to assay directly the binding of the IR alphaCT peptide to an IR construct (IR485) consisting of the three N-terminal domains of the receptor monomer. Our measurements show further that the binding of the IR alphaCT peptide to IR485 competes with the binding of a prototypical "Site 1" insulin mimetic peptide to the same receptor fragment. The competitive nature of their binding appears to be reflected in a previously undetected sequence similarity between the IR alphaCT peptide and the Site 1 mimetic peptide. In contrast, a prototypical "Site 2" peptide has very limited affinity for IR485. Taken together, these results complement our recent observation that there is a possible structural relationship between these mimetic peptides and insulin itself. They also add support to the view that the segment of unexplained electron density lying on the surface of the central beta-sheet of the L1 domain in the IR ectodomain crystal structure arises from the IR alphaCT peptide. Finally, we show that mutation of the critical IR alphaCT peptide residue Phe714 to alanine does not affect the peptide's affinity for IR485 and conclude that the resultant loss of insulin binding with this mutation results from loss of interaction of the phenylalanine side chain with insulin.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1520-4995
pubmed:author
pubmed:issnType
Electronic
pubmed:day
16
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5492-500
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
A thermodynamic study of ligand binding to the first three domains of the human insulin receptor: relationship between the receptor alpha-chain C-terminal peptide and the site 1 insulin mimetic peptides.
pubmed:affiliation
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't