PDBsum entry 4o2f

Immune system

PDB id: 4o2f

Contents

Protein chains

274 a.a.

99 a.a.

Ligands

HIS-VAL-ALA-VAL-GLU-ASN-ALA-LEU ×2

Waters ×882

PDB id:

4o2f

Name:

Immune system

Title:

A peptide complexed with hla-b 3901

Structure:

Hla class i histocompatibility antigen, b-39 alpha chain. Chain: a, d. Fragment: unp residues 25-298. Synonym: mhc class i antigen b 39. Engineered: yes. Beta-2-microglobulin. Chain: b, e. Synonym: beta-2-microglobulin form pi 5.3. Engineered: yes.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: hla-b, hlab. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: b2m, cdabp0092, hdcma22p. Synthetic: yes. Organism_taxid: 9606

Resolution:

1.90Å R-factor: 0.187 R-free: 0.213

Authors:

M.Sun,J.Liu,J.Qi,B.Tefsen,Y.Shi,J.Yan,G.F.Gao

Key ref:

M.Sun et al. (2014). Nα-terminal acetylation for T cell recognition: molecular basis of MHC class I-restricted nα-acetylpeptide presentation. J Immunol, 192, 5509-5519. PubMed id: 24829406 DOI: 10.4049/jimmunol.1400199

Date:

17-Dec-13 Release date: 23-Jul-14

Protein chains

P01889  (1B07_HUMAN) -  HLA class I histocompatibility antigen, B alpha chain from Homo sapiens

Seq: 362 a.a.

Struc: 274 a.a.*

Protein chains

P61769  (B2MG_HUMAN) -  Beta-2-microglobulin from Homo sapiens

Seq: 119 a.a.

Struc: 99 a.a.

* PDB and UniProt seqs differ at 15 residue positions (black crosses)

DOI no: 10.4049/jimmunol.1400199

J Immunol 192:5509-5519 (2014)

PubMed id: 24829406

Nα-terminal acetylation for T cell recognition: molecular basis of MHC class I-restricted nα-acetylpeptide presentation.

M.Sun, J.Liu, J.Qi, B.Tefsen, Y.Shi, J.Yan, G.F.Gao.

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.