1emo: Difference between revisions
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==Overview== | ==Overview== | ||
The nuclear magnetic resonance structure of a covalently linked pair of, calcium-binding (cb) epidermal growth factor-like (EGF) domains from human, fibrillin-1, the protein defective in the Marfan syndrome, is described., The two domains are in a rigid, rod-like arrangement, stabilized by, interdomain calcium binding and hydrophobic interactions. We propose a, model for the arrangement of fibrillin monomers in microfibrils that, reconciles structural and antibody binding data, and we describe a set of, disease-causing mutations that provide the first clues to the specificity, of cbEFG interactions. The residues involved in stabilizing the domain, linkage are highly conserved in fibrillin, fibulin, thrombomodulin, and, the low density lipoprotein receptor. We propose that the relative, orientation of tandem cbEGF domains in these proteins is similar, but that, in others, including Notch, pairs adopt a completely different, conformation. | The nuclear magnetic resonance structure of a covalently linked pair of, calcium-binding (cb) epidermal growth factor-like (EGF) domains from human, fibrillin-1, the protein defective in the Marfan syndrome, is described., The two domains are in a rigid, rod-like arrangement, stabilized by, interdomain calcium binding and hydrophobic interactions. We propose a, model for the arrangement of fibrillin monomers in microfibrils that, reconciles structural and antibody binding data, and we describe a set of, disease-causing mutations that provide the first clues to the specificity, of cbEFG interactions. The residues involved in stabilizing the domain, linkage are highly conserved in fibrillin, fibulin, thrombomodulin, and, the low density lipoprotein receptor. We propose that the relative, orientation of tandem cbEGF domains in these proteins is similar, but that, in others, including Notch, pairs adopt a completely different, conformation. | ||
==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: signal]] | [[Category: signal]] | ||
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Revision as of 17:38, 12 November 2007
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NMR STUDY OF A PAIR OF FIBRILLIN CA2+ BINDING EPIDERMAL GROWTH FACTOR-LIKE DOMAINS, 22 STRUCTURES
OverviewOverview
The nuclear magnetic resonance structure of a covalently linked pair of, calcium-binding (cb) epidermal growth factor-like (EGF) domains from human, fibrillin-1, the protein defective in the Marfan syndrome, is described., The two domains are in a rigid, rod-like arrangement, stabilized by, interdomain calcium binding and hydrophobic interactions. We propose a, model for the arrangement of fibrillin monomers in microfibrils that, reconciles structural and antibody binding data, and we describe a set of, disease-causing mutations that provide the first clues to the specificity, of cbEFG interactions. The residues involved in stabilizing the domain, linkage are highly conserved in fibrillin, fibulin, thrombomodulin, and, the low density lipoprotein receptor. We propose that the relative, orientation of tandem cbEGF domains in these proteins is similar, but that, in others, including Notch, pairs adopt a completely different, conformation.
DiseaseDisease
Known diseases associated with this structure: Aortic aneurysm, ascending, and dissection OMIM:[134797], Ectopia lentis, familial OMIM:[134797], MASS syndrome OMIM:[134797], Marfan syndrome OMIM:[134797], Shprintzen-Goldberg syndrome OMIM:[134797], Weill-Marchesani syndrome, dominant OMIM:[134797]
About this StructureAbout this Structure
1EMO is a Single protein structure of sequence from Homo sapiens with CA as ligand. Structure known Active Sites: CA1 and CA2. Full crystallographic information is available from OCA.
ReferenceReference
Solution structure of a pair of calcium-binding epidermal growth factor-like domains: implications for the Marfan syndrome and other genetic disorders., Downing AK, Knott V, Werner JM, Cardy CM, Campbell ID, Handford PA, Cell. 1996 May 17;85(4):597-605. PMID:8653794
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