5E9D: Rd-1 Mart-1 High Bound To Mart-1 Decameric Peptide (ela) In Complex With Hla-a2

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 alphabeta 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.
PDB ID: 5E9DDownload
MMDB ID: 139888
PDB Deposition Date: 2015/10/15
Updated in MMDB: 2016/07
Experimental Method:
x-ray diffraction
Resolution: 2.51  Å
Source Organism:
Similar Structures:
Biological Unit for 5E9D: pentameric; determined by author and by software (PISA)
Molecular Components in 5E9D
Label Count Molecule
Proteins (5 molecules)
HLA Class I Histocompatibility Antigen, A-2 Alpha Chain(Gene symbol: HLA-A)
Molecule annotation
Beta-2-microglobulin(Gene symbol: B2M)
Molecule annotation
Melanoma Derived Mart-1 Peptide
Molecule annotation
A6-tcr Valpha
Molecule annotation
A6-tcr Vbeta
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB