PDBsum entry 5e9d

Protein binding

PDB id: 5e9d

Contents

Protein chains

266 a.a.

98 a.a.

110 a.a.

115 a.a.

Ligands

GLU-LEU-ALA-GLY-ILE-GLY-ILE-LEU-THR-VAL ×2

Waters ×73

PDB id:

5e9d

Name:

Protein binding

Title:

Rd-1 mart-1 high bound to mart-1 decameric peptide (ela) in complex with hla-a2

Structure:

Hla class i histocompatibility antigen, a-2 alpha chain. Chain: a, f. Synonym: mhc class i antigen a 2. Engineered: yes. Beta-2-microglobulin. Chain: b, g. Engineered: yes. Melanoma derived mart-1 peptide. Chain: c, h.

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. Gene: trav12-2.

Resolution:

2.51Å R-factor: 0.183 R-free: 0.232

Authors:

N.K.Singh,B.M.Baker

Key ref:

D.T.Harris et al. (2016). An Engineered Switch in T Cell Receptor Specificity Leads to an Unusual but Functional Binding Geometry. Structure, 24, 1142-1154. PubMed id: 27238970 DOI: 10.1016/j.str.2016.04.011

Date:

15-Oct-15 Release date: 08-Jun-16

Protein chains

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

Seq: 365 a.a.

Struc: 266 a.a.*

Protein chains

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

Seq: 119 a.a.

Struc: 98 a.a.

Protein chains

A0A075B6T6  (TVAL2_HUMAN) -  T cell receptor alpha variable 12-2 from Homo sapiens

Seq: 113 a.a.

Struc: 110 a.a.*

Protein chains

A0A0K0K1A5  (TVB65_HUMAN) -  T cell receptor beta variable 6-5 from Homo sapiens

Seq: 114 a.a.

Struc: 115 a.a.*

* PDB and UniProt seqs differ at 29 residue positions (black crosses)

DOI no: 10.1016/j.str.2016.04.011

Structure 24:1142-1154 (2016)

PubMed id: 27238970

An Engineered Switch in T Cell Receptor Specificity Leads to an Unusual but Functional Binding Geometry.

D.T.Harris, N.K.Singh, Q.Cai, S.N.Smith, C.W.Vander Kooi, E.Procko, D.M.Kranz, B.M.Baker.

ABSTRACT

Utilizing a diverse binding site, T cell receptors (TCRs) specifically recognize a composite ligand comprised of a foreign peptide and a major histocompatibility complex protein (MHC). To help understand the determinants of TCR specificity, we studied a parental and engineered receptor whose peptide specificity had been switched via molecular evolution. Altered specificity was associated with a significant change in TCR-binding geometry, but this did not impact the ability of the TCR to signal in an antigen-specific manner. The determinants of binding and specificity were distributed among contact and non-contact residues in germline and hypervariable loops, and included disruption of key TCR-MHC interactions that bias αβ TCRs toward particular binding modes. Sequence-fitness landscapes identified additional mutations that further enhanced specificity. Our results demonstrate that TCR specificity arises from the distributed action of numerous sites throughout the interface, with significant implications for engineering therapeutic TCRs with novel and functional recognition properties.