4O2E

A peptide complexed with HLA-B*3901

Summary for 4O2E

• Entry DOI: 10.2210/pdb4o2e/pdb
• Related: 4O2C 4O2F
• Descriptor: HLA class I histocompatibility antigen, B-39 alpha chain, Beta-2-microglobulin, Peptide from ATP-dependent RNA helicase DDX3X, ... (4 entities in total)
• Functional Keywords: ig-like, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Membrane; Single-pass type I membrane protein: P30475; Secreted: P61769; Nucleus speckle: O00571
• Total number of polymer chains: 6
• Total formula weight: 88806.13

Authors

Sun, M.,Liu, J.,Qi, J.,Tefsen, B.,Shi, Y.,Yan, J.,Gao, G.F. (deposition date: 2013-12-17, release date: 2014-07-23, Last modification date: 2024-10-30)

Primary citation

Sun, M.,Liu, J.,Qi, J.,Tefsen, B.,Shi, Y.,Yan, J.,Gao, G.F.
N alpha-terminal acetylation for T cell recognition: molecular basis of MHC class I-restricted n alpha-acetylpeptide presentation
J.Immunol., 192:5509-5519, 2014

PubMed Abstract: As one of the most common posttranslational modifications (PTMs) of eukaryotic proteins, N(α)-terminal acetylation (Nt-acetylation) generates a class of N(α)-acetylpeptides that are known to be presented by MHC class I at the cell surface. Although such PTM plays a pivotal role in adjusting proteolysis, the molecular basis for the presentation and T cell recognition of N(α)-acetylpeptides remains largely unknown. In this study, we determined a high-resolution crystallographic structure of HLA (HLA)-B*3901 complexed with an N(α)-acetylpeptide derived from natural cellular processing, also in comparison with the unmodified-peptide complex. Unlike the α-amino-free P1 residues of unmodified peptide, of which the α-amino group inserts into pocket A of the Ag-binding groove, the N(α)-linked acetyl of the acetylated P1-Ser protrudes out of the groove for T cell recognition. Moreover, the Nt-acetylation not only alters the conformation of the peptide but also switches the residues in the α1-helix of HLA-B*3901, which may impact the T cell engagement. The thermostability measurements of complexes between N(α)-acetylpeptides and a series of MHC class I molecules derived from different species reveal reduced stability. Our findings provide the insight into the mode of N(α)-acetylpeptide-specific presentation by classical MHC class I molecules and shed light on the potential of acetylepitope-based immune intervene and vaccine development.

PubMed: 24829406
DOI: 10.4049/jimmunol.1400199

Experimental method

X-RAY DIFFRACTION (1.981 Å)