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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
11
|
| pubmed:dateCreated |
1997-3-17
|
| pubmed:abstractText |
Recombinant wild-type human IGF-1 and a C-region mutant in which residues 28-37 have been replaced by a 4-glycine bridge (4-Gly IGF-1) were secreted and purified from yeast. An IGF-1 analogue in which residues 29-41 of the C-region have been deleted (mini IGF-1) was created by site-directed mutagenesis and also expressed. All three proteins adopted the insulin-fold as determined by circular dichroism. The significantly raised expression levels of mini IGF-1 allowed the recording of two-dimensional NMR spectra. The affinity of 4-Gly IGF-1 for the IGF-1 receptor was approximately 100-fold lower than that of wild-type IGF-1 and the affinity for the insulin receptor was approximately 10-fold lower. Mini IGF-1 showed no affinity for either receptor. Not only does the C-region of IGF-1 contribute directly to the free energy of binding to the IGF-1 receptor, but also the absence of flexibility in this region eliminates binding altogether. As postulated for the binding of insulin to its own receptor, it is proposed that binding of IGF-1 to the IGF-1 receptor also involves a conformational change in which the C-terminal B-region residues detach from the body of the molecule to expose the underlying A-region residues.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Nov
|
| pubmed:issn |
0269-2139
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
9
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1011-9
|
| pubmed:dateRevised |
2009-11-19
|
| pubmed:meshHeading |
pubmed-meshheading:8961354-Amino Acid Sequence,
pubmed-meshheading:8961354-Animals,
pubmed-meshheading:8961354-Chromatography, High Pressure Liquid,
pubmed-meshheading:8961354-Circular Dichroism,
pubmed-meshheading:8961354-Cloning, Molecular,
pubmed-meshheading:8961354-Computer Simulation,
pubmed-meshheading:8961354-Humans,
pubmed-meshheading:8961354-Insulin-Like Growth Factor I,
pubmed-meshheading:8961354-Male,
pubmed-meshheading:8961354-Models, Molecular,
pubmed-meshheading:8961354-Molecular Sequence Data,
pubmed-meshheading:8961354-Peptide Fragments,
pubmed-meshheading:8961354-Protein Binding,
pubmed-meshheading:8961354-Protein Engineering,
pubmed-meshheading:8961354-Protein Folding,
pubmed-meshheading:8961354-Rats,
pubmed-meshheading:8961354-Rats, Sprague-Dawley,
pubmed-meshheading:8961354-Receptor, IGF Type 1,
pubmed-meshheading:8961354-Recombinant Proteins,
pubmed-meshheading:8961354-Saccharomyces cerevisiae
|
| pubmed:year |
1996
|
| pubmed:articleTitle |
Engineering the C-region of human insulin-like growth factor-1: implications for receptor binding.
|
| pubmed:affiliation |
Department of Crystallography, Birkbeck College, London.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|