6BXP

Crystal Structure of HLA-B*57:01 with a modified HIV peptide RKV-Kyn

Summary for 6BXP

• Entry DOI: 10.2210/pdb6bxp/pdb
• Descriptor: HLA class I histocompatibility antigen, B-57 alpha chain, Beta-2-microglobulin, HIV peptide RKV-Kyn, ... (5 entities in total)
• Functional Keywords: immunopeptidome, kynurenine, hiv, ptm, hla-b*57:01, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 44937.99

Authors

Gras, S.,Rossjohn, J. (deposition date: 2017-12-18, release date: 2018-03-14, Last modification date: 2024-11-20)

Primary citation

Ramarathinam, S.H.,Gras, S.,Alcantara, S.,Yeung, A.W.S.,Mifsud, N.A.,Sonza, S.,Illing, P.T.,Glaros, E.N.,Center, R.J.,Thomas, S.R.,Kent, S.J.,Ternette, N.,Purcell, D.F.J.,Rossjohn, J.,Purcell, A.W.
Identification of Native and Posttranslationally Modified HLA-B*57:01-Restricted HIV Envelope Derived Epitopes Using Immunoproteomics.
Proteomics, 18:e1700253-e1700253, 2018

PubMed Abstract: The recognition of pathogen-derived peptides by T lymphocytes is the cornerstone of adaptive immunity, whereby intracellular antigens are degraded in the cytosol and short peptides assemble with class I human leukocyte antigen (HLA) molecules in the ER. These peptide-HLA complexes egress to the cell surface and are scrutinized by cytotoxic CD8+ T-cells leading to the eradication of the infected cell. Here, naturally presented HLA-B*57:01 bound peptides derived from the envelope protein of the human immunodeficiency virus (HIVenv) are identified. HIVenv peptides are present at a very small percentage of the overall HLA-B*57:01 peptidome (<0.1%) and both native and posttranslationally modified forms of two distinct HIV peptides are identified. Notably, a peptide bearing a natively encoded C-terminal tryptophan residue is also present in a modified form containing a kynurenine residue. Kynurenine is a major product of tryptophan catabolism and is abundant during inflammation and infection. Binding of these peptides at a molecular level and their immunogenicity in preliminary functional studies are examined. Modest immune responses are observed to the modified HIVenv peptide, highlighting a potential role for kynurenine-modified peptides in the immune response to HIV and other viral infections.

PubMed: 29437277
DOI: 10.1002/pmic.201700253

Experimental method

X-RAY DIFFRACTION (1.45 Å)