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(New page: ==HLA-C*06:02 presenting VRSRR(ABA)LRL== <StructureSection load='5w67' size='340' side='right' caption='5w67, resolution 2.30Å' scene=''> == Structural highlights...)
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Revision as of 10:45, 13 September 2017
proteopedia linkproteopedia linkHLA-C*06:02 presenting VRSRR(ABA)LRL
Structural highlights
Disease[1C06_HUMAN] Disease susceptibility is associated with variations affecting the gene represented in this entry. [B2MG_HUMAN] Defects in B2M are the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:241600]. Affected individuals show marked reduction in serum concentrations of immunoglobulin and albumin, probably due to rapid degradation.[1] Note=Beta-2-microglobulin may adopt the fibrillar configuration of amyloid in certain pathologic states. The capacity to assemble into amyloid fibrils is concentration dependent. Persistently high beta(2)-microglobulin serum levels lead to amyloidosis in patients on long-term hemodialysis.[2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] Function[1C06_HUMAN] Involved in the presentation of foreign antigens to the immune system. [B2MG_HUMAN] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. Publication Abstract from PubMedHuman Leucocyte antigen (HLA) C*06:02 is identified as the allele associated with the highest risk for the development of the autoimmune skin disease psoriasis. However, the diversity and mode of peptide presentation by the HLA-C*06:02 molecule remains unclear. Here, we describe the endogenous peptide repertoire of approximately 3,000 sequences for HLA-C*06:02 that defines the peptide-binding motif for this HLA allomorph. We found that HLA-C*06:02 predominantly presents nonamer peptides with dominant arginine anchors at the P2 & P7 positions and a preference for small hydrophobic residues at the C-terminus (Pomega). To determine the structural basis of this selectivity, we determined crystal structures of HLA-C*06:02 in complex with two self-peptides (ARTELYRSL and ARFNDLRFV) and an analogue of a melanocyte auto-antigen (ADAMTSL5, VRSRR-abu-LRL) implicated in psoriasis. These structures revealed that HLA-C*06:02 possesses a deep peptide-binding groove comprising two electronegative B- and E-pockets that coincide with the preference for P2 and P7 arginine anchors. The ADAMTSL5 autoantigen possessed a P7-Leu instead of the P7-Arg residue, but nevertheless was accommodated within the HLA-C*06:02 antigen-binding cleft. Collectively, our results provide the structural basis for understanding peptide repertoire selection in HLA-C*06:02. The molecular basis for peptide repertoire selection in the Human Leucocyte Antigen (HLA) C*06:02 molecule.,Mobbs JI, Illing PT, Dudek NL, Brooks AG, Baker DG, Purcell AW, Rossjohn J, Vivian JP J Biol Chem. 2017 Aug 30. pii: jbc.M117.806976. doi: 10.1074/jbc.M117.806976. PMID:28855257[15] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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