6WL3

preTCRbeta-pMHC complex crystal structure

Summary for 6WL3

• Entry DOI: 10.2210/pdb6wl3/pdb
• Descriptor: H-2 class I histocompatibility antigen, K-B alpha chain, ARG-GLY-TYR-LEU-TYR-GLN-GLY-LEU, N15 preTCR beta (3 entities in total)
• Functional Keywords: pretcr, h-2kb, t cell development, beta selection, immune system
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 9
• Total formula weight: 149221.19

Authors

Li, X.,Mallis, R.J.,Mizsei, R.,Tan, K.,Reinherz, E.L.,Wang, J. (deposition date: 2020-04-18, release date: 2020-12-23, Last modification date: 2024-10-23)

Primary citation

Li, X.,Mizsei, R.,Tan, K.,Mallis, R.J.,Duke-Cohan, J.S.,Akitsu, A.,Tetteh, P.W.,Dubey, A.,Hwang, W.,Wagner, G.,Lang, M.J.,Arthanari, H.,Wang, J.H.,Reinherz, E.L.
Pre-T cell receptors topologically sample self-ligands during thymocyte beta-selection.
Science, 371:181-185, 2021

PubMed Abstract: Self-discrimination, a critical but ill-defined molecular process programmed during thymocyte development, requires myriad pre-T cell receptors (preTCRs) and αβTCRs. Using x-ray crystallography, we show how a preTCR applies the concave β-sheet surface of its single variable domain (Vβ) to "horizontally" grab the protruding MHC α2-helix. By contrast, αβTCRs purpose all six complementarity-determining region (CDR) loops of their paired VαVβ module to recognize peptides bound to major histocompatibility complex molecules (pMHCs) in "vertical" head-to-head binding. The preTCR topological fit ensures that CDR3β reaches the peptide's featured C-terminal segment for pMHC sampling, establishing the subsequent αβTCR canonical docking mode. "Horizontal" docking precludes germline CDR1β- and CDR2β-MHC binding to broaden β-chain repertoire diversification before αβTCR-mediated selection refinement. Thus, one subunit successively attunes the recognition logic of related multicomponent receptors.

PubMed: 33335016
DOI: 10.1126/science.abe0918

Experimental method

X-RAY DIFFRACTION (3.45 Å)