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| - | [[Image:2dtg.gif|left|200px]]<br /> | + | #REDIRECT [[4zxb]] This PDB entry is obsolete and replaced by 4zxb |
| - | <applet load="2dtg" size="450" color="white" frame="true" align="right" spinBox="true"
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| - | caption="2dtg, resolution 3.80Å" />
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| - | '''Insulin receptor (IR) ectodomain in complex with fab's'''<br />
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| - | ==Overview==
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| - | The insulin receptor is a phylogenetically ancient tyrosine kinase, receptor found in organisms as primitive as cnidarians and insects. In, higher organisms it is essential for glucose homeostasis, whereas the, closely related insulin-like growth factor receptor (IGF-1R) is involved, in normal growth and development. The insulin receptor is expressed in two, isoforms, IR-A and IR-B; the former also functions as a high-affinity, receptor for IGF-II and is implicated, along with IGF-1R, in malignant, transformation. Here we present the crystal structure at 3.8 A resolution, of the IR-A ectodomain dimer, complexed with four Fabs from the monoclonal, antibodies 83-7 and 83-14 (ref. 4), grown in the presence of a fragment of, an insulin mimetic peptide. The structure reveals the domain arrangement, in the disulphide-linked ectodomain dimer, showing that the insulin, receptor adopts a folded-over conformation that places the ligand-binding, regions in juxtaposition. This arrangement is very different from previous, models. It shows that the two L1 domains are on opposite sides of the, dimer, too far apart to allow insulin to bind both L1 domains, simultaneously as previously proposed. Instead, the structure implicates, the carboxy-terminal surface of the first fibronectin type III domain as, the second binding site involved in high-affinity binding.
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| - | ==Disease==
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| - | Known diseases associated with this structure: Diabetes mellitus, insulin-resistant, with acanthosis nigricans OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147670 147670]], Hyperinsulinemic hypoglycemia, familial, 5 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147670 147670]], Leprechaunism OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147670 147670]], Rabson-Mendenhall syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147670 147670]]
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| - | ==About this Structure==
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| - | 2DTG is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Active as [http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2DTG OCA].
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| - | ==Reference==
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| - | Structure of the insulin receptor ectodomain reveals a folded-over conformation., McKern NM, Lawrence MC, Streltsov VA, Lou MZ, Adams TE, Lovrecz GO, Elleman TC, Richards KM, Bentley JD, Pilling PA, Hoyne PA, Cartledge KA, Pham TM, Lewis JL, Sankovich SE, Stoichevska V, Da Silva E, Robinson CP, Frenkel MJ, Sparrow LG, Fernley RT, Epa VC, Ward CW, Nature. 2006 Sep 14;443(7108):218-21. Epub 2006 Sep 6. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16957736 16957736]
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| - | [[Category: Homo sapiens]]
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| - | [[Category: Mus musculus]]
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| - | [[Category: Receptor protein-tyrosine kinase]]
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| - | [[Category: Single protein]]
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| - | [[Category: Lawrence, M.C.]]
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| - | [[Category: Streltsov, V.A.]]
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| - | [[Category: insulin receptor; ir ectodomain; x-ray crystallography]]
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| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 21:39:53 2007''
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