| Structural and biological properties of the Drosophila insulin-like peptide 5 show evolutionary conservation. | |
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MedLine Citation:
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PMID: 20974844 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We report the crystal structure of two variants of Drosophila melanogaster insulin-like peptide 5 (DILP5) at a resolution of 1.85 Å. DILP5 shares the basic fold of the insulin peptide family (T conformation) but with a disordered B-chain C terminus. DILP5 dimerizes in the crystal and in solution. The dimer interface is not similar to that observed in vertebrates, i.e. through an anti-parallel β-sheet involving the B-chain C termini but, in contrast, is formed through an anti-parallel β-sheet involving the B-chain N termini. DILP5 binds to and activates the human insulin receptor and lowers blood glucose in rats. It also lowers trehalose levels in Drosophila. Reciprocally, human insulin binds to the Drosophila insulin receptor and induces negative cooperativity as in the human receptor. DILP5 also binds to insect insulin-binding proteins. These results show high evolutionary conservation of the insulin receptor binding properties despite divergent insulin dimerization mechanisms. |
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Authors:
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Waseem Sajid; Nikolaj Kulahin; Gerd Schluckebier; Ulla Ribel; Hope Rosalind Henderson; Marc Tatar; Bo Falck Hansen; Angela Manegold Svendsen; Vladislav V Kiselyov; Per Nørgaard; Per-Olof Wahlund; Jakob Brandt; Ronald A Kohanski; Asser Sloth Andersen; Pierre De Meyts |
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Publication Detail:
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Type: Journal Article Date: 2010-10-25 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 286 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-01-03 Completed Date: 2011-01-31 Revised Date: 2012-01-09 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 661-73 Citation Subset: IM |
Affiliation:
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Receptor Systems Biology Laboratory, Insulin and Incretin Biology, Hagedorn Research Institute, 2820 Gentofte, Denmark. |
| Data Bank Information | |
Bank Name/Acc. No.:
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PDB/2WFU; 2WFV |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adipocytes
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drug effects,
metabolism Amino Acid Sequence Animals Blood Glucose / metabolism Conserved Sequence* Crystallography, X-Ray Drosophila melanogaster* Evolution, Molecular* Female Humans Insulin / chemistry*, metabolism*, pharmacology Iodine Radioisotopes Lipogenesis / drug effects Male Mice Models, Molecular Molecular Sequence Data Protein Conformation Proteins / chemistry*, metabolism*, pharmacology Rats Receptor, Insulin / metabolism Trehalose / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Blood Glucose; 0/Insulin; 0/Iodine Radioisotopes; 0/Leydig insulin-like protein; 0/Proteins; 99-20-7/Trehalose; EC 2.7.10.1/Receptor, Insulin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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