PDBsum entry 4mnq

Immune system

PDB id: 4mnq

Contents

Protein chains

276 a.a.

100 a.a.

200 a.a.

240 a.a.

Ligands

ILE-LEU-ALA-LYS-PHE-LEU-HIS-TRP-LEU

GOL

EDO ×2

Waters ×21

PDB id:

4mnq

Name:

Immune system

Title:

Tcr-peptide specificity overrides affinity enhancing tcr-mhc interactions

Structure:

Hla class i histocompatibility antigen, a-2 alpha chain. Chain: a. Synonym: mhc class i antigen a 2. Engineered: yes. Beta-2-microglobulin. Chain: b. Synonym: beta-2-microglobulin form pi 5.3. Engineered: yes. Telomerase reverse transcriptase.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: hla-a, hlaa. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: b2m, cdabp0092, hdcma22p. Synthetic: yes. Other_details: mage htert 540-548 sequence.

Resolution:

2.74Å R-factor: 0.218 R-free: 0.284

Authors:

P.J.Rizkallah,D.K.Cole,A.K.Sewell,B.K.Jakobsen

Key ref:

D.K.Cole et al. (2014). T-cell receptor (TCR)-peptide specificity overrides affinity-enhancing TCR-major histocompatibility complex interactions. J Biol Chem, 289, 628-638. PubMed id: 24196962 DOI: 10.1074/jbc.M113.522110

Date:

11-Sep-13 Release date: 13-Nov-13

Protein chain

P04439  (1A03_HUMAN) -  HLA class I histocompatibility antigen, A alpha chain from Homo sapiens

Seq: 365 a.a.

Struc: 276 a.a.*

Protein chain

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

Seq: 119 a.a.

Struc: 100 a.a.*

Protein chain

H2RG00  (H2RG00_PANTR) -  Ig-like domain-containing protein from Pan troglodytes

Seq: 185 a.a.

Struc: 200 a.a.*

Protein chain

K7N5N2  (K7N5N2_HUMAN) -  T-cell receptor, sp3.4 alpha chain from Homo sapiens

Seq: 207 a.a.

Struc: 200 a.a.*

Protein chain

P01850  (TRBC1_HUMAN) -  T cell receptor beta constant 1 from Homo sapiens

Seq: 176 a.a.

Struc: 240 a.a.*

* PDB and UniProt seqs differ at 186 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains : E.C.2.7.7.49 - RNA-directed Dna polymerase.
• Reaction: DNA(n) + a 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) + diphosphate

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

Added reference

DOI no: 10.1074/jbc.M113.522110

J Biol Chem 289:628-638 (2014)

PubMed id: 24196962

T-cell receptor (TCR)-peptide specificity overrides affinity-enhancing TCR-major histocompatibility complex interactions.

D.K.Cole, K.M.Miles, F.Madura, C.J.Holland, A.J.Schauenburg, A.J.Godkin, A.M.Bulek, A.Fuller, H.J.Akpovwa, P.G.Pymm, N.Liddy, M.Sami, Y.Li, P.J.Rizkallah, B.K.Jakobsen, A.K.Sewell.

ABSTRACT

αβ T-cell receptors (TCRs) engage antigens using complementarity-determining region (CDR) loops that are either germ line-encoded (CDR1 and CDR2) or somatically rearranged (CDR3). TCR ligands compose a presentation platform (major histocompatibility complex (MHC)) and a variable antigenic component consisting of a short "foreign" peptide. The sequence of events when the TCR engages its peptide-MHC (pMHC) ligand remains unclear. Some studies suggest that the germ line elements of the TCR engage the MHC prior to peptide scanning, but this order of binding is difficult to reconcile with some TCR-pMHC structures. Here, we used TCRs that exhibited enhanced pMHC binding as a result of mutations in either CDR2 and/or CDR3 loops, that bound to the MHC or peptide, respectively, to dissect the roles of these loops in stabilizing TCR-pMHC interactions. Our data show that TCR-peptide interactions play a strongly dominant energetic role providing a binding mode that is both temporally and energetically complementary with a system requiring positive selection by self-pMHC in the thymus and rapid recognition of non-self-pMHC in the periphery.