1uzp: Difference between revisions
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==Overview== | ==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. | 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== | |||
Known diseases associated with this structure: Aortic aneurysm, ascending, and dissection OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134797 134797]], Ectopia lentis, familial OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134797 134797]], MASS syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134797 134797]], Marfan syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134797 134797]], Shprintzen-Goldberg syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134797 134797]], Weill-Marchesani syndrome, dominant OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134797 134797]] | |||
==About this Structure== | ==About this Structure== | ||
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[[Category: tb domain]] | [[Category: tb domain]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 19:40:33 2007'' | ||