The Human C1q Globular Domain: Structure and Recognition of Non-Immune Self Ligands

Groupe IRPAS, Institut de Biologie Structurale Grenoble, France.
Frontiers in Immunology 11/2011; 2:92. DOI: 10.3389/fimmu.2011.00092
Source: PubMed


C1q, the ligand-binding unit of the C1 complex of complement, is a pattern recognition molecule with the unique ability to sense an amazing variety of targets, including a number of altered structures from self, such as apoptotic cells. The three-dimensional structure of its C-terminal globular domain, responsible for its recognition function, has been solved by X-ray crystallography, revealing a tightly packed heterotrimeric assembly with marked differences in the surface patterns of the subunits, and yielding insights into its versatile binding properties. In conjunction with other approaches, this same technique has been used recently to decipher the mechanisms that allow this domain to interact with various non-immune self ligands, including molecules known to provide eat-me signals on apoptotic cells, such as phosphatidylserine and DNA. These investigations provide evidence for a common binding area for these ligands located in subunit C of the C1q globular domain, and suggest that ligand recognition through this area down-regulates C1 activation, hence contributing to the control of the inflammatory reaction. The purpose of this article is to give an overview of these advances which represent a first step toward understanding the recognition mechanisms of C1q and their biological implications.

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    • "3.7. IgG4-Fc can assemble into an Fc-Fc mediated hexamer The C1q component of complement has a hexameric arrangement , and activates the classical complement pathway through binding to IgM and IgG immune complexes (Burton, 1990; Ghai et al., 2007; Gaboriaud et al., 2012). An IgM hexamer (or pentamer with J-chain) can activate complement (Randall et al., 1990). "
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    • "Arginine residue plays an important role in ligand binding functional activity as reported by the X-ray analysis of lectin [37]. In this aspect, the presence of Arg-14 and Arg-66 in cattle, buffalo, nilgai, and blackbuck replacing Glu-14 and Thr-66 of sheep and goat in the coiled and lectin domain, respectively, may explain the variation in strength of ligand binding activity. "
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    ABSTRACT: Conglutinin, a collagenous C-type lectin, acts as soluble pattern recognition receptor (PRR) in recognition of pathogens. In the present study, genes encoding neck and carbohydrate recognition domain (NCRD) of conglutinin in goat and blackbuck were amplified, cloned, and sequenced. The obtained 488 bp ORFs encoding NCRD were submitted to NCBI with accession numbers KC505182 and KC505183. Both nucleotide and predicted amino acid sequences were analysed with sequences of other ruminants retrieved from NCBI GenBank using DNAstar and Megalign5.2 software. Sequence analysis revealed maximum similarity of blackbuck sequence with wild ruminants like nilgai and buffalo, whereas goat sequence displayed maximum similarity with sheep sequence at both nucleotide and amino acid level. Phylogenetic analysis further indicated clear divergence of wild ruminants from the domestic ruminants in separate clusters. The predicted secondary structures of NCRD protein in goat and blackbuck using SWISSMODEL ProtParam online software were found to possess 6 beta-sheets and 3 alpha-helices which are identical to the result obtained in case of sheep, cattle, buffalo, and nilgai. However, quaternary structure in goat, sheep, and cattle was found to differ from that of buffalo, nilgai, and blackbuck, suggesting a probable variation in the efficiency of antimicrobial activity among wild and domestic ruminants.
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    • "In some of these cases work is underway (e.g. (Dobo et al., 2009; Gaboriaud et al., 2011; Garlatti et al., 2010; Gout et al., 2011; Jenkins et al., 2006; Lang et al., 2010; Teillet et al., 2008) that is likely to give insight into the higher order assembly and perhaps its is this that will provide the structural focus at the meeting in 2014. Other questions remaining include generating a molecular understanding of how MAC pore formation is regulated by CD59, how the different convertases achieve specificity of activity and regulation and, particularly with the wealth of GWAS and other genetic studies, what are the molecular bases of the many genetic susceptibilities now associated with complement proteins? "
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