PDBsum entry 5e8n

Immune system

PDB id: 5e8n

Contents

Protein chains

272 a.a.

99 a.a.

258 a.a.

Ligands

MET-CYS-LEU-ARG-MET-THR-ALA-VAL-MET ×4

GOL

SO4

Waters ×135

PDB id:

5e8n

Name:

Immune system

Title:

The structure of the teipp associated trh4 peptide in complex with h- 2d(b)

Structure:

H-2 class i histocompatibility antigen, d-b alpha chain. Chain: a, d, g, j. Synonym: h-2d(b). Engineered: yes. Beta-2-microglobulin. Chain: b, e, h, k. Engineered: yes. Ceramide synthase 5. Chain: c, f, i, l.

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Gene: h2-d1. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: b2m. Synthetic: yes. Organism_taxid: 10090

Resolution:

2.25Å R-factor: 0.242 R-free: 0.286

Authors:

I.Hafstrand,E.Doorduijn,A.D.Duru,J.Buratto,C.C.Oliveira,T.Sandalova, T.Van Hall,A.Achour

Key ref:

I.Hafstrand et al. (2016). The MHC Class I Cancer-Associated Neoepitope Trh4 Linked with Impaired Peptide Processing Induces a Unique Noncanonical TCR Conformer. J Immunol, 196, 2327-2334. PubMed id: 26800871 DOI: 10.4049/jimmunol.1502249

Date:

14-Oct-15 Release date: 03-Feb-16

Protein chains

P01899  (HA11_MOUSE) -  H-2 class I histocompatibility antigen, D-B alpha chain from Mus musculus

Seq: 362 a.a.

Struc: 272 a.a.

Protein chains

P01887  (B2MG_MOUSE) -  Beta-2-microglobulin from Mus musculus

Seq: 119 a.a.

Struc: 99 a.a.*

Protein chain

P01899  (HA11_MOUSE) -  H-2 class I histocompatibility antigen, D-B alpha chain from Mus musculus

Seq: 362 a.a.

Struc: 258 a.a.

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: Chains : E.C.2.3.1.24 - sphingosine N-acyltransferase.
• Reaction: a fatty acyl-CoA + sphing-4-enine = an N-acylsphing-4-enine + CoA + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.4049/jimmunol.1502249

J Immunol 196:2327-2334 (2016)

PubMed id: 26800871

The MHC Class I Cancer-Associated Neoepitope Trh4 Linked with Impaired Peptide Processing Induces a Unique Noncanonical TCR Conformer.

I.Hafstrand, E.M.Doorduijn, A.D.Duru, J.Buratto, C.C.Oliveira, T.Sandalova, T.van Hall, A.Achour.

ABSTRACT

MHC class I downregulation represents a significant challenge for successful T cell-based immunotherapy. T cell epitopes associated with impaired peptide processing (TEIPP) constitute a novel category of immunogenic Ags that are selectively presented on transporter associated with Ag processing-deficient cells. The TEIPP neoepitopes are CD8 T cell targets, derived from nonmutated self-proteins that might be exploited to prevent immune escape. In this study, the crystal structure of H-2D(b) in complex with the first identified TEIPP Ag (MCLRMTAVM) derived from the Trh4 protein has been determined to 2.25 Å resolution. In contrast to prototypic H-2D(b) peptides, Trh4 takes a noncanonical peptide-binding pattern with extensive sulfur-π interactions that contribute to the overall complex stability. Importantly, the noncanonical methionine at peptide position 5 acts as a main anchor, altering only the conformation of the H-2D(b) residues Y156 and H155 and thereby forming a unique MHC/peptide conformer that is essential for recognition by TEIPP-specific T cells. Substitution of peptide residues p2C and p5M to the conservative α-aminobutyric acid and norleucine, respectively, significantly reduced complex stability, without altering peptide conformation or T cell recognition. In contrast, substitution of p5M to a conventional asparagine abolished recognition by the H-2D(b)/Trh4-specific T cell clone LnB5. We anticipate that the H-2D(b)/Trh4 complex represents the first example, to our knowledge, of a broader repertoire of alternative MHC class I binders.