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User:Janice C. Telfer/Group B SRCR domains

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Group 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.

Group B SRCR domain

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 spirochete 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 [2], but only a subset of them participate in the immune response to Leptospira [6]. 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 [7].

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.

  1. 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
  2. 2.0 2.1 Herzig CT, Baldwin CL. Genomic organization and classification of the bovine WC1 genes and expression by peripheral blood gamma delta T cells. BMC Genomics. 2009 Apr 24;10:191. PMID:19393067 doi:10.1186/1471-2164-10-191
  3. Herzig CT, Waters RW, Baldwin CL, Telfer JC. Evolution of the CD163 family and its relationship to the bovine gamma delta T cell co-receptor WC1. BMC Evol Biol. 2010 Jun 15;10:181. PMID:20550670 doi:10.1186/1471-2148-10-181
  4. Rodamilans B, Munoz IG, Bragado-Nilsson E, Sarrias MR, Padilla O, Blanco FJ, Lozano F, Montoya G. Crystal structure of the third extracellular domain of CD5 reveals the fold of a group B scavenger cysteine-rich receptor domain. J Biol Chem. 2007 Apr 27;282(17):12669-77. Epub 2007 Feb 23. PMID:17322294 doi:10.1074/jbc.M611699200
  5. Wang F, Herzig C, Ozer D, Baldwin CL, Telfer JC. Tyrosine phosphorylation of scavenger receptor cysteine-rich WC1 is required for the WC1-mediated potentiation of TCR-induced T-cell proliferation. Eur J Immunol. 2009 Jan;39(1):254-66. PMID:19130552 doi:10.1002/eji.200838472
  6. Rogers AN, Vanburen DG, Hedblom EE, Tilahun ME, Telfer JC, Baldwin CL. Gammadelta T cell function varies with the expressed WC1 coreceptor. J Immunol. 2005 Mar 15;174(6):3386-93. PMID:15749871
  7. Chen C, Herzig CT, Telfer JC, Baldwin CL. Antigenic basis of diversity in the gammadelta T cell co-receptor WC1 family. Mol Immunol. 2009 Aug;46(13):2565-75. Epub 2009 Jun 17. PMID:19539374 doi:10.1016/j.molimm.2009.05.010

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Janice C. Telfer

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