1uzk: Difference between revisions

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|PDB= 1uzk |SIZE=350|CAPTION= <scene name='initialview01'>1uzk</scene>, resolution 1.35&Aring;
|PDB= 1uzk |SIZE=350|CAPTION= <scene name='initialview01'>1uzk</scene>, resolution 1.35&Aring;
|SITE= <scene name='pdbsite=AC1:Ca+Binding+Site+For+Chain+A'>AC1</scene>
|SITE= <scene name='pdbsite=AC1:Ca+Binding+Site+For+Chain+A'>AC1</scene>
|LIGAND= <scene name='pdbligand=CA:CALCIUM ION'>CA</scene>
|LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>
|ACTIVITY=  
|ACTIVITY=  
|GENE=  
|GENE=  
|DOMAIN=
|RELATEDENTRY=
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1uzk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uzk OCA], [http://www.ebi.ac.uk/pdbsum/1uzk PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1uzk RCSB]</span>
}}
}}


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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: Lee, S S.J.]]
[[Category: Lee, S S.J.]]
[[Category: Stuart, D I.]]
[[Category: Stuart, D I.]]
[[Category: CA]]
[[Category: calcium]]
[[Category: calcium]]
[[Category: cbegf domain]]
[[Category: cbegf domain]]
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[[Category: tb domain]]
[[Category: tb domain]]


''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:39:00 2008''
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:17:35 2008''