1uzk

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File:1uzk.gif


PDB ID 1uzk

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, resolution 1.35Å
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Ligands: ,
Resources: FirstGlance, OCA, PDBsum, RCSB
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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.

About this StructureAbout this Structure

1UZK is a Single protein structure of sequence from Homo sapiens. 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

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