6UZ1

Noncanonical binding of single-chain A6 TCR variant S3-4 in complex with Tax/HLA-A2

Summary for 6UZ1

• Entry DOI: 10.2210/pdb6uz1/pdb
• Descriptor: MHC class I antigen, A-2 alpha chain, Beta-2-microglobulin, LEU-LEU-PHE-GLY-TYR-PRO-VAL-TYR-VAL, ... (7 entities in total)
• Functional Keywords: single-chain t cell receptor, peptide major histocompatibility complex, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 10
• Total formula weight: 139082.73

Authors

Ma, J.,Singh, N.K. (deposition date: 2019-11-14, release date: 2020-10-28, Last modification date: 2024-10-30)

Primary citation

Singh, N.K.,Alonso, J.A.,Harris, D.T.,Anderson, S.D.,Ma, J.,Hellman, L.M.,Rosenberg, A.M.,Kolawole, E.M.,Evavold, B.D.,Kranz, D.M.,Baker, B.M.
An Engineered T Cell Receptor Variant Realizes the Limits of Functional Binding Modes.
Biochemistry, 59:4163-4175, 2020

PubMed Abstract: T cell receptors (TCRs) orchestrate cellular immunity by recognizing peptides presented by a range of major histocompatibility complex (MHC) proteins. Naturally occurring TCRs bind the composite peptide/MHC surface, recognizing peptides that are structurally and chemically compatible with the TCR binding site. Here we describe a molecularly evolved TCR variant that binds the human class I MHC protein HLA-A2 independent of the bound peptide, achieved by a drastic perturbation of the TCR binding geometry that places the molecule far from the peptide binding groove. This unique geometry is unsupportive of normal T cell signaling. A substantial divergence between affinity measurements in solution and in two dimensions between proximal cell membranes leads us to attribute the lack of signaling to steric hindrance that limits binding in the confines of a cell-cell interface. Our results provide an example of how receptor binding geometry can impact T cell function and provide further support for the view that germline-encoded residues in TCR binding loops evolved to drive productive TCR recognition and signaling.

PubMed: 33074657
DOI: 10.1021/acs.biochem.0c00689

Experimental method

X-RAY DIFFRACTION (3.14 Å)