1uzk
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INTEGRIN BINDING CBEGF22-TB4-CBEGF33 FRAGMENT OF HUMAN FIBRILLIN-1, CA BOUND TO CBEGF23 DOMAIN ONLY
OverviewOverview
Human fibrillin-1, the major structural protein of extracellular matrix, (ECM) 10-12 nm microfibrils, is dominated by 43 calcium binding epidermal, growth factor-like (cbEGF) and 7 transforming growth factor beta binding, protein-like (TB) domains. Crystal structures reveal the integrin binding, cbEGF22-TB4-cbEGF23 fragment of human fibrillin-1 to be a, Ca(2+)-rigidified tetragonal pyramid. We suggest that other cbEGF-TB pairs, within the fibrillins may adopt a similar orientation to cbEGF22-TB4. In, addition, we have located a flexible RGD integrin binding loop within TB4., Modeling, cell attachment and spreading assays, immunocytochemistry, and, surface plasmon resonance indicate that cbEGF22 bound to TB4 is a, requirement for integrin activation and provide insight into the molecular, basis of the fibrillin-1 interaction with alphaVbeta3. In light of our, data, we propose a novel model for the assembly of the fibrillin, microfibril and a mechanism to explain its extensibility.
DiseaseDisease
Known diseases associated with this structure: Aortic aneurysm, ascending, and dissection OMIM:[134797], Ectopia lentis, familial OMIM:[134797], MASS syndrome OMIM:[134797], Marfan syndrome OMIM:[134797], Shprintzen-Goldberg syndrome OMIM:[134797], Weill-Marchesani syndrome, dominant OMIM:[134797]
About this StructureAbout this Structure
1UZK is a Single protein structure of sequence from Homo sapiens with CA as ligand. Structure known Active Site: AC1. Full crystallographic information is available from OCA.
ReferenceReference
Structure of the integrin binding fragment from fibrillin-1 gives new insights into microfibril organization., Lee SS, Knott V, Jovanovic J, Harlos K, Grimes JM, Choulier L, Mardon HJ, Stuart DI, Handford PA, Structure. 2004 Apr;12(4):717-29. PMID:15062093
Page seeded by OCA on Mon Nov 12 19:40:31 2007