1uzk: Difference between revisions
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==Overview== | ==Overview== | ||
Human fibrillin-1, the major structural protein of extracellular matrix | 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. | ||
==Disease== | ==Disease== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Handford, P | [[Category: Handford, P A.]] | ||
[[Category: Harlos, K.]] | [[Category: Harlos, K.]] | ||
[[Category: Knott, V.]] | [[Category: Knott, V.]] | ||
[[Category: Lee, S | [[Category: Lee, S S.J.]] | ||
[[Category: Stuart, D | [[Category: Stuart, D I.]] | ||
[[Category: CA]] | [[Category: CA]] | ||
[[Category: calcium]] | [[Category: calcium]] | ||
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[[Category: tb domain]] | [[Category: tb domain]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:30:08 2008'' | ||
