Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Query: UNIPROT:P01889 (
ankylosing spondylitis
)
5,717
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
A highly significant association was found between the bovine MHC class I antigen BoLA-A8 and a form of vertebral osteophytosis/
ankylosing spondylitis
known as chronic posterior spinal paresis (PSP) in Holstein bulls (P < 0.001). In a population study, restricted to unrelated bulls, BoLA-A8 was significantly associated with PSP (P = 0.0015) with a relative risk of 34.6. In a family study, one PSP bull, BoLA A8/A20, sired 13 offspring. BoLA-A8 was significantly associated with PSP (P = 0.0008). All five PSP sons inherited the A8 allele and the eight healthy sons each inherited the A20 allele. In three other families a complete association of BoLA-A8 and PSP was observed. Lod score analysis, using all available families, indicated a significant linkage between BoLA and PSP (lod score = 6.9). Based on clinical observation, pathology, age/sex predilection, and a strong association with a class I
MHC molecule
, this inflammatory disease appears analogous to the human condition known as
ankylosing spondylitis
.
...
PMID:Association between the bovine major histocompatibility complex and chronic posterior spinal paresis--a form of ankylosing spondylitis--in Holstein bulls. 849 13
Conformational changes of major histocompatibility complex (MHC) antigens have the potential to be recognized by T cells and may arise from polymorphic variation of the
MHC molecule
, the binding of modifying ligands, or both. Here, we investigated whether metal ions could affect allele-dependent structural variation of the two minimally distinct human leukocyte antigen (HLA)-B*27:05 and HLA-B*27:09 subtypes, which exhibit differential association with the rheumatic disease
ankylosing spondylitis
(AS). We employed NMR spectroscopy and X-ray crystallography coupled with ensemble refinement to study the AS-associated HLA-B*27:05 subtype and the AS-nonassociated HLA-B* 27:09 in complex with the self-peptide pVIPR (RRKWRRWHL). Both techniques revealed that pVIPR exhibits a higher degree of flexibility when complexed with HLA-B*27:05 than with HLA-B*27:09. Furthermore, we found that the binding of the metal ion Cu
2+
or Ni
2+
, but not Mn
2+
, Zn
2+
, or Hg
2+
, affects the structure of a pVIPR-bound HLA-B*27 molecule in a subtype-dependent manner. In HLA-B*27:05, the metals triggered conformational reorientations of pVIPR, but no such structural changes were observed in the HLA-B*27:09 subtype, with or without bound metal ion. These observations provide the first demonstration that not only major histocompatibility complex class II, but also class I, molecules can undergo metal ion-induced conformational alterations. Our findings suggest that metals may have a role in triggering rheumatic diseases such as AS and also have implications for the molecular basis of metal-induced hypersensitivities and allergies.
...
PMID:Metal-triggered conformational reorientation of a self-peptide bound to a disease-associated HLA-B*27 subtype. 3129 58
