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'''INTEGRIN BINDING CBEGF22-TB4-CBEGF33 FRAGMENT OF HUMAN FIBRILLIN-1, CA BOUND TO CBEGF23 DOMAIN ONLY''' | '''INTEGRIN BINDING CBEGF22-TB4-CBEGF33 FRAGMENT OF HUMAN FIBRILLIN-1, CA BOUND TO CBEGF23 DOMAIN ONLY''' | ||
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[[Category: Lee, S S.J.]] | [[Category: Lee, S S.J.]] | ||
[[Category: Stuart, D I.]] | [[Category: Stuart, D I.]] | ||
[[Category: | [[Category: Calcium]] | ||
[[Category: | [[Category: Cbegf domain]] | ||
[[Category: | [[Category: Disease mutation]] | ||
[[Category: | [[Category: Egf-like domain]] | ||
[[Category: | [[Category: Extra-cellular matrix]] | ||
[[Category: | [[Category: Extracellular matrix]] | ||
[[Category: | [[Category: Fibrillin-1]] | ||
[[Category: | [[Category: Glycoprotein]] | ||
[[Category: | [[Category: Polymorphism]] | ||
[[Category: | [[Category: Tb domain]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 11:54:26 2008'' | |||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | |||
Revision as of 08:54, 3 May 2008
INTEGRIN BINDING CBEGF22-TB4-CBEGF33 FRAGMENT OF HUMAN FIBRILLIN-1, CA BOUND TO CBEGF23 DOMAIN ONLY
Overview
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 Structure
1UZK is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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 Sat May 3 11:54:26 2008
