4O2E: A Peptide Complexed With Hla-b*3901

As one of the most common posttranslational modifications (PTMs) of eukaryotic proteins, N(alpha)-terminal acetylation (Nt-acetylation) generates a class of N(alpha)-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(alpha)-acetylpeptides remains largely unknown. In this study, we determined a high-resolution crystallographic structure of HLA (HLA)-B*3901 complexed with an N(alpha)-acetylpeptide derived from natural cellular processing, also in comparison with the unmodified-peptide complex. Unlike the alpha-amino-free P1 residues of unmodified peptide, of which the alpha-amino group inserts into pocket A of the Ag-binding groove, the N(alpha)-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 alpha1-helix of HLA-B*3901, which may impact the T cell engagement. The thermostability measurements of complexes between N(alpha)-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(alpha)-acetylpeptide-specific presentation by classical MHC class I molecules and shed light on the potential of acetylepitope-based immune intervene and vaccine development.
PDB ID: 4O2EDownload
MMDB ID: 121717
PDB Deposition Date: 2013/12/17
Updated in MMDB: 2014/07
Experimental Method:
x-ray diffraction
Resolution: 1.98  Å
Source Organism:
Similar Structures:
Biological Unit for 4O2E: trimeric; determined by author and by software (PISA)
Molecular Components in 4O2E
Label Count Molecule
Proteins (3 molecules)
HLA Class I Histocompatibility Antigen, B-39 Alpha Chain(Gene symbol: HLA-B)
Molecule annotation
Beta-2-microglobulin(Gene symbol: B2M)
Molecule annotation
Peptide From Atp-dependent RNA Helicase Ddx3x(Gene symbol: DDX3X)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB