1XWE

NMR Structure of C345C (NTR) domain of C5 of complement

Summary for 1XWE

• Entry DOI: 10.2210/pdb1xwe/pdb
• NMR Information: BMRB: 6001
• Descriptor: Complement C5 (1 entity in total)
• Functional Keywords: ob fiold, signaling protein
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P01031
• Total number of polymer chains: 1
• Total formula weight: 17146.54

Authors

Bramham, J.,Thai, C.-T.,Soares, D.C.,Uhrin, D.,Ogata, R.T.,Barlow, P.N. (deposition date: 2004-10-30, release date: 2004-12-21, Last modification date: 2024-10-16)

Primary citation

Bramham, J.,Thai, C.-T.,Soares, D.C.,Uhrin, D.,Ogata, R.T.,Barlow, P.N.
Functional Insights from the Structure of the Multifunctional C345C Domain of C5 of Complement
J.Biol.Chem., 280:10636-10645, 2005

PubMed Abstract: 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.

PubMed: 15598652
DOI: 10.1074/jbc.M413126200

Experimental method

SOLUTION NMR