1zlg
From Proteopedia
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Solution structure of the extracellular matrix protein anosmin-1
Contents |
Overview
Kallmann's syndrome corresponds to a loss of sense of smell and, hypogonadotrophic hypogonadism. Defects in anosmin-1 result in the, X-linked inherited form of Kallmann's syndrome. Anosmin-1 is an, extracellular matrix protein comprised of an N-terminal, cysteine-rich, (Cys-box) domain and a whey acidic protein-like (WAP) domain, followed by, four fibronectin type III (FnIII) domains. The solution structures of, recombinant proteins containing the first three domains (PIWF1) and all, six domains (PIWF4) were determined by X-ray scattering and analytical, ultracentrifugation. Guinier analyses showed that PIWF1 and PIWF4 have, different radii of gyration (R(G)) values of 3.1 nm and 6.7 nm, respectively, but similar cross-sectional radii of gyration (R(XS)) values, of 1.5 nm and 1.9 nm, respectively. Distance distribution functions showed, that the maximum lengths of PIWF1 and PIWF4 were 11 nm and 23 nm, respectively. Analytical ultracentrifugation gave sedimentation, coefficients of 2.52 S and 3.55 S for PIWF1 and PIWF4, respectively. The, interpretation of the scattering data by constrained modelling requires, homology models for all six domains in anosmin-1. While models were, already available for the WAP and FnIII domains, searches suggested the, Cys-box domain may resemble the cysteine-rich region of the insulin-like, growth factor receptor. Automated constrained molecular modelling based on, joining the anosmin-1 domains with structurally randomised linkers, resulted in 10,000 models for anosmin-1. A trial-and-error search showed, that about 0.1-1.4% of these models fitted the X-ray data. The best models, showed that the three domains and six domains in PIWF1 and PIWF4, respectively, were extended. The inter-domain linkers in anosmin-1 could, not all be extended at the same time, and there was evidence for, inter-domain flexibility. Models with folded-back domain arrangements do, not fit the data. These solution structures account for the known, biological function of anosmin-1, in particular its ability to interact, with its three macromolecular ligands.
Disease
Known diseases associated with this structure: Kallmann syndrome OMIM:[308700]
About this Structure
1ZLG is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Extended and flexible domain solution structure of the extracellular matrix protein anosmin-1 by X-ray scattering, analytical ultracentrifugation and constrained modelling., Hu Y, Sun Z, Eaton JT, Bouloux PM, Perkins SJ, J Mol Biol. 2005 Jul 15;350(3):553-70. PMID:15949815
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