| Structural highlights
1of2 is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | ,
| | Related: | 1a1m, 1a1n, 1a1o, 1a6z, 1a9b, 1a9e, 1agb, 1agc, 1agd, 1age, 1agf, 1akj, 1ao7, 1ce6, 1de4, 1e27, 1e28, 1efx, 1exu, 1gzp, 1gzq, 1hhg, 1hhh, 1hhi, 1hhj, 1hhk, 1hla, 1hsa, 1hsb, 1i4f, 1i7r, 1i7t, 1i7u, 1im3, 1im9, 1jf1, 1jht, 1jnj, 1k5n, 1kpr, 1ktl, 1lds, 1qlf, 1qqd, 1tmc, 2clr, 2hla, 3hla, 1jge, 1oga, 1ogt |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Disease
[1B27_HUMAN] Defects in HLA-B are a cause of susceptibility to spondyloarthropathy type 1 (SPDA1) [MIM:106300]. It is a chronic rheumatic disease with multifactorial inheritance. It includes a spectrum of related disorders comprising ankylosing spondylitis, a subset of psoriatic arthritis, reactive arthritis (e.g. Reiter syndrome), arthritis associated with inflammatory bowel disease and undifferentiated spondyloarthropathy. These disorders may occur simultaneously or sequentially in the same patient, probably representing various phenotypic expressions of the same disease. Ankylosing spondylitis is the form of rheumatoid arthritis affecting the spine and is considered the prototype of seronegative spondyloarthropathies. It produces pain and stiffness as a result of inflammation of the sacroiliac, intervertebral, and costovertebral joints. Note=In the Greek Cypriot population, a restricted number of HLA-B27 subtypes are associated with ankylosing spondylitis and other B27-related diseases and an elevated frequency of the B*2702 allele in ankylosing spondylitis patients is identified. The allele B*2707 seems to have a protective role in this population because it was found only in the healthy controls.[1]
Function
[1B27_HUMAN] Involved in the presentation of foreign antigens to the immune system. [VIPR1_HUMAN] This is a receptor for VIP. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. The affinity is VIP = PACAP-27 > PACAP-38.[2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The products of the human leukocyte antigen subtypes HLA-B*2705 and HLA-B*2709 differ only in residue 116 (Asp vs. His) within the peptide binding groove but are differentially associated with the autoimmune disease ankylosing spondylitis (AS); HLA-B*2705 occurs in AS-patients, whereas HLA-B*2709 does not. The subtypes also generate differential T cell repertoires as exemplified by distinct T cell responses against the self-peptide pVIPR (RRKWRRWHL). The crystal structures described here show that pVIPR binds in an unprecedented dual conformation only to HLA-B*2705 molecules. In one binding mode, peptide pArg5 forms a salt bridge to Asp116, connected with drastically different interactions between peptide and heavy chain, contrasting with the second, conventional conformation, which is exclusively found in the case of B*2709. These subtype-dependent differences in pVIPR binding link the emergence of dissimilar T cell repertoires in individuals with HLA-B*2705 or HLA-B*2709 to the buried Asp116/His116 polymorphism and provide novel insights into peptide presentation by major histocompatibility antigens.
Dual, HLA-B27 subtype-dependent conformation of a self-peptide.,Hulsmeyer M, Fiorillo MT, Bettosini F, Sorrentino R, Saenger W, Ziegler A, Uchanska-Ziegler B J Exp Med. 2004 Jan 19;199(2):271-81. PMID:14734527[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Varnavidou-Nicolaidou A, Karpasitou K, Georgiou D, Stylianou G, Kokkofitou A, Michalis C, Constantina C, Gregoriadou C, Kyriakides G. HLA-B27 in the Greek Cypriot population: distribution of subtypes in patients with ankylosing spondylitis and other HLA-B27-related diseases. The possible protective role of B*2707. Hum Immunol. 2004 Dec;65(12):1451-4. PMID:15603872 doi:10.1016/j.humimm.2004.08.177
- ↑ Xia M, Sreedharan SP, Goetzl EJ. Predominant expression of type II vasoactive intestinal peptide receptors by human T lymphoblastoma cells: transduction of both Ca2+ and cyclic AMP signals. J Clin Immunol. 1996 Jan;16(1):21-30. PMID:8926282
- ↑ Hulsmeyer M, Fiorillo MT, Bettosini F, Sorrentino R, Saenger W, Ziegler A, Uchanska-Ziegler B. Dual, HLA-B27 subtype-dependent conformation of a self-peptide. J Exp Med. 2004 Jan 19;199(2):271-81. PMID:14734527 doi:10.1084/jem.20031690
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