User:Janice C. Telfer/Group B SRCR domains
Group B Scavenger Receptor Cysteine-Rich (SRCR) DomainsGroup B Scavenger Receptor Cysteine-Rich (SRCR) Domains
Members of the group B SRCR domain family include CD5, CD6, DMBT1, Spα, WC1, CD163A, CD163b, and CD163c-α. (reviewed in [1][2] [3]) Some of these (i.e. WC1 and CD163c-α) are multi-gene families.
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Group B SRCR domains are 100-110 amino acids long and are characterized by 6-8 cysteines, with conserved spacing. Disulfide bonds are formed between cysteines 1 and 4, 2 and 7, 3 and 8, and 5 and 6. Cysteines 2 and/or 7 are missing in some group B SRCR domains, resulting in the loss of one of the potential disulfide bonds. The crystal structure of the third SRCR domain of human CD5, which contains 8 cysteines, shows four disulfide bonds [4].
Group B SRCR domains bind to both protein and non-petidic ligands. In the latter class of ligands are molecules found on bacteria, such as lipopolysaccharide (LPS) and lipoteichoic acid (LTA), which suggests that group B SRCR proteins play a role in the host immune response to microorganisms. The group B SRCR domain family member WC1 appears to play an important role in the bovine response to the spirochaete Leptospira as a co-receptor whose tyrosine phosphorylation is required for optimal gamma delta T cell response [5]. There are approximately 15 different WC1 genes in the bovine genome [6], but only a subset of them participate in the immune response to Leptospira [7]. This subset is labelled by an antibody recognizing the first WC1 cloned, known as WC1.1. A subset labelled by an antibody recognizing the second WC1 cloned, known as WC1.2, does not participate in the immune response to Leptospira. Anti-WC1-1 recognizes SRCR domain 1 of WC1-1, WC1-3, WC1-11 and WC1-nd1; anti-WC1.2 recognizes SRCR domain 1 of WC1-4 and WC1-9 [8].
The extracellular domain of WC1 proteins contain 11 SRCR domains with a unique N-terminal SRCR domain (1a) and a duplicated SRCR cassette (i.e. 1a-(2b-3c-4d-5e-6d)-(7b-8c-9d-10e-11d'). Most of the diversity between WC1 genes is contained in the first SRCR domain, and thus the first SRCR domain of WC1 is the most likely candidate for interaction with micoorganisms such as Leptospira. Models of the structure of these domains were generated using alignments of WC1 SRCR 1a domains with the third domain of human CD5 and the alignment mode of the Swiss-Model server (http://swissmodel.expasy.org/). Variable regions between WC1 SRCR 1a domains are indicated in dark grey. Cysteines are indicated in black and disulfide bonds are shown in yellow. The loop implicated in bacterial binding by DMBT1 and CD163A is shown in mesh ribbon.
- ↑ Sarrias MR, Gronlund J, Padilla O, Madsen J, Holmskov U, Lozano F. The Scavenger Receptor Cysteine-Rich (SRCR) domain: an ancient and highly conserved protein module of the innate immune system. Crit Rev Immunol. 2004;24(1):1-37. PMID:14995912
- ↑ Herzig,C.T. and C.L. Baldwin 2009 BMC Genomics 10:191
- ↑ Herzig,C.T. et. al. 2010 Evol. Biol. 10:181.
- ↑ Rodamilans, B. et. al. 2007 J. Biol. Chem. 282:12669-77 doi M611699200 [pii]10.1074/jbc.M611699200.
- ↑ Wang, F. et al 2009 Eur. J. Immunol. 39:254-66.
- ↑ Herzig,C.T. and C.L. Baldwin 2009 BMC Genomics 10:191.
- ↑ Rogers,A.N. et al 2005 J. Immunol. 174:3386-93.
- ↑ Chen, C. et al 2009 Mol. Immunol. 46:2565-75.