This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
1lmj
From Proteopedia
OCA (Talk | contribs)
(New page: 200px<br /> <applet load="1lmj" size="450" color="white" frame="true" align="right" spinBox="true" caption="1lmj" /> '''NMR Study of the Fibrillin-1 cbEGF12-13 Pai...)
Next diff →
Revision as of 15:56, 12 November 2007
|
NMR Study of the Fibrillin-1 cbEGF12-13 Pair of Ca2+ Binding Epidermal Growth Factor-like Domains
Contents |
Overview
Fibrillin-1 is a mosaic protein mainly composed of 43 calcium binding, epidermal growth factor-like (cbEGF) domains arranged as multiple, tandem, repeats. Mutations within the fibrillin-1 gene cause Marfan syndrome, (MFS), a heritable disease of connective tissue. More than 60% of, MFS-causing mutations identified are localized to cbEGFs, emphasizing that, the native properties of these domains are critical for fibrillin-1, function. The cbEGF12-13 domain pair is within the longest run of cbEGFs, and many mutations that cluster in this region are associated with severe, neonatal MFS. The NMR solution structure of Ca(2+)-loaded cbEGF12-13, exhibits a near-linear, rod-like arrangement of domains. This observation, supports the hypothesis that all fibrillin-1 (cb)EGF-cbEGF pairs, characterized by a single interdomain linker residue, possess this, rod-like structure. The domain arrangement of cbEGF12-13 is stabilized by, additional interdomain packing interactions to those observed for, cbEGF32-33, which may help to explain the previously reported higher, calcium binding affinity of cbEGF13. Based on this structure, a model of, cbEGF11-15 that encompasses all known neonatal MFS missense mutations has, highlighted a potential binding region. Backbone dynamics data confirm the, extended structure of cbEGF12-13 and lend support to the hypothesis that a, correlation exists between backbone flexibility and cbEGF domain calcium, affinity. These results provide important insight into the potential, consequences of MFS-associated mutations for the assembly and, biomechanical properties of connective tissue microfibrils.
Disease
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 Structure
1LMJ is a Single protein structure of sequence from Homo sapiens with CA as ligand. Full crystallographic information is available from OCA.
Reference
Solution structure and dynamics of a calcium binding epidermal growth factor-like domain pair from the neonatal region of human fibrillin-1., Smallridge RS, Whiteman P, Werner JM, Campbell ID, Handford PA, Downing AK, J Biol Chem. 2003 Apr 4;278(14):12199-206. Epub 2003 Jan 2. PMID:12511552
Page seeded by OCA on Mon Nov 12 18:02:33 2007
