1xwe
From Proteopedia
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'''NMR Structure of C345C (NTR) domain of C5 of complement''' | '''NMR Structure of C345C (NTR) domain of C5 of complement''' | ||
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[[Category: Thai, C T.]] | [[Category: Thai, C T.]] | ||
[[Category: Uhrin, D.]] | [[Category: Uhrin, D.]] | ||
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Revision as of 12:35, 3 May 2008
NMR Structure of C345C (NTR) domain of C5 of complement
Contents |
Overview
The complement protein C5 initiates assembly of the membrane attack complex. This remarkable process results in lysis of target cells and is fundamental to mammalian defense against infection. The 150-amino acid residue domain at the C terminus of C5 (C5-C345C) is pivotal to C5 function. It interacts with enzymes that convert C5 to C5b, the first step in the assembly of the membrane attack complex; it also binds to the membrane attack complex components C6 and C7 with high affinity. Here a recombinant version of this C5-C345C domain is shown to adopt the oligosaccharide/oligonucleotide binding fold, with two helices packed against a five-stranded beta-barrel. The structure is compared with those from the netrin-like module family that have a similar fold. Residues critical to the interaction with C5-convertase cluster on a mobile, hydrophobic inter-strand loop that protrudes from the open face of the beta-barrel. The opposite, helix-dominated face of C5-C345C carries a pair of exposed hydrophobic side chains adjacent to a striking negatively charged patch, consistent with affinity for positively charged factor I modules in C6 and C7. Modeling of homologous domains from complement proteins C3 and C4, which do not participate in membrane attack complex assembly, suggests that this provisionally identified C6/C7-interacting face is indeed specific to C5.
Disease
Known disease associated with this structure: C5 deficiency OMIM:[120900]
About this Structure
1XWE is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Functional insights from the structure of the multifunctional C345C domain of C5 of complement., Bramham J, Thai CT, Soares DC, Uhrin D, Ogata RT, Barlow PN, J Biol Chem. 2005 Mar 18;280(11):10636-45. Epub 2004 Dec 14. PMID:15598652 Page seeded by OCA on Sat May 3 15:35:23 2008
