1emo
NMR STUDY OF A PAIR OF FIBRILLIN CA2+ BINDING EPIDERMAL GROWTH FACTOR-LIKE DOMAINS, 22 STRUCTURES
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| Sites: | and | ||||||
| Ligands: | |||||||
| Gene: | FBN1 (Homo sapiens) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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. 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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