3OX8

Crystal Structure of HLA A*02:03 Bound to HBV Core 18-27

Summary for 3OX8

• Entry DOI: 10.2210/pdb3ox8/pdb
• Related: 3OXR 3OXS
• Descriptor: MHC class I antigen, Beta-2-microglobulin, 10mer peptide from Pre-core-protein, ... (4 entities in total)
• Functional Keywords: protein-peptide complex, host-virus interaction, immunogenicity, therapeutic design, tcr recognition, helix, beta-sheet, antigen presentation, peptide binding, cell surface, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: P61769
• Total number of polymer chains: 6
• Total formula weight: 90043.83

Authors

Liu, J.,Chen, Y.,Lai, L.,Ren, E. (deposition date: 2010-09-21, release date: 2011-05-04, Last modification date: 2024-10-30)

Primary citation

Liu, J.,Chen, K.Y.,Ren, E.C.
Structural insights into the binding of hepatitis B virus core peptide to HLA-A2 alleles: Towards designing better vaccines.
Eur.J.Immunol., 41:2097-2106, 2011

PubMed Abstract: Binding of specific antigenic peptides with human leukocyte antigen (HLA) molecules is a prerequisite for the initiation of T-cell responses and structural information about the peptide-HLA complex is essential for the detailed understanding of such interactions. HLA-A2 is the most prevalent HLA allele globally but aside from A*02:01 there is a significant lack of crystal structures, particularly for alleles that occur in high frequencies among Asian populations. Here, we report three HLA-A2 structures with the immunodominant hepatitis B core antigen 18-27 (HBcAg18-27) epitope, namely A*02:03, A*02:06, and A*02:07 at resolutions of 2.16, 1.70, and 1.75 Å respectively. This comparative analysis reveals that minor polymorphic residue changes between different HLA alleles can induce significant alterations in the major histocompatibility complex-peptide interface, and introduce conformational changes in the p3-p8 peptide region. Circular dichroism analysis demonstrated the HLA-A2-peptide complexes to have a hierarchy of thermostability and binding affinity in the order of A*02:06>A*02:07>A*02:01>A*02:03. Our findings provide structural insights into the varied HLA-A2 allele binding of the hepatitis B core antigen 18-27 epitope and the data suggest that chemical modifications of the peptide side chains could be a promising strategy to modulate and improve HLA-A2-peptide binding affinity for vaccine design.

PubMed: 21538979
DOI: 10.1002/eji.201041370

Experimental method

X-RAY DIFFRACTION (2.16 Å)