5W6A

HLA-C*06:02 presenting ARTELYRSL

Summary for 5W6A

• Entry DOI: 10.2210/pdb5w6a/pdb
• Related: 5w67 5w69
• Descriptor: HLA class I histocompatibility antigen, Cw-6 alpha chain, Beta-2-microglobulin, ALA-ARG-THR-GLU-LEU-TYR-ARG-SER-LEU, ... (4 entities in total)
• Functional Keywords: hla, antigen presentation, human leukocyte antigen, immune system
• Biological source: Homo sapiens (Human); More
• Cellular location: Membrane; Single-pass type I membrane protein: Q29963; Secreted . Note=(Microbial infection) In the presence of M: P61769
• Total number of polymer chains: 6
• Total formula weight: 90153.60

Authors

Mobbs, J.I.,Vivian, J.P.,Rossjohn, J. (deposition date: 2017-06-16, release date: 2017-08-23, Last modification date: 2023-10-04)

Primary citation

Mobbs, J.I.,Illing, P.T.,Dudek, N.L.,Brooks, A.G.,Baker, D.G.,Purcell, A.W.,Rossjohn, J.,Vivian, J.P.
The molecular basis for peptide repertoire selection in the human leucocyte antigen (HLA) C*06:02 molecule.
J. Biol. Chem., 292:17203-17215, 2017

PubMed Abstract: Human leukocyte 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 ∼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 and P7 positions and a preference for small hydrophobic residues at the C terminus (PΩ). 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 autoantigen (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.

PubMed: 28855257
DOI: 10.1074/jbc.M117.806976

Experimental method

X-RAY DIFFRACTION (1.74 Å)