6wl3

preTCRbeta-pMHC complex crystal structurepreTCRbeta-pMHC complex crystal structure

Structural highlights

6wl3 is a 9 chain structure with sequence from Mus musculus and Vesicular stomatitis virus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.45Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

HA1B_MOUSE Involved in the presentation of foreign antigens to the immune system.

Publication Abstract from PubMed

Self-discrimination, a critical but ill-defined molecular process programmed during thymocyte development, requires myriad pre-T cell receptors (preTCRs) and alphabetaTCRs. Using x-ray crystallography, we show how a preTCR applies the concave beta-sheet surface of its single variable domain (Vbeta) to "horizontally" grab the protruding MHC alpha2-helix. By contrast, alphabetaTCRs purpose all six complementarity-determining region (CDR) loops of their paired ValphaVbeta module to recognize peptides bound to major histocompatibility complex molecules (pMHCs) in "vertical" head-to-head binding. The preTCR topological fit ensures that CDR3beta reaches the peptide's featured C-terminal segment for pMHC sampling, establishing the subsequent alphabetaTCR canonical docking mode. "Horizontal" docking precludes germline CDR1beta- and CDR2beta-MHC binding to broaden beta-chain repertoire diversification before alphabetaTCR-mediated selection refinement. Thus, one subunit successively attunes the recognition logic of related multicomponent receptors.

Pre-T cell receptors topologically sample self-ligands during thymocyte beta-selection.,Li X, Mizsei R, Tan K, Mallis RJ, Duke-Cohan JS, Akitsu A, Tetteh PW, Dubey A, Hwang W, Wagner G, Lang MJ, Arthanari H, Wang JH, Reinherz EL Science. 2021 Jan 8;371(6525):181-185. doi: 10.1126/science.abe0918. Epub 2020 , Dec 17. PMID:33335016^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Li X, Mizsei R, Tan K, Mallis RJ, Duke-Cohan JS, Akitsu A, Tetteh PW, Dubey A, Hwang W, Wagner G, Lang MJ, Arthanari H, Wang JH, Reinherz EL. Pre-T cell receptors topologically sample self-ligands during thymocyte β-selection. Science. 2021 Jan 8;371(6525):181-185. PMID:33335016 doi:10.1126/science.abe0918

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OCA

[1] Li X, Mizsei R, Tan K, Mallis RJ, Duke-Cohan JS, Akitsu A, Tetteh PW, Dubey A, Hwang W, Wagner G, Lang MJ, Arthanari H, Wang JH, Reinherz EL. Pre-T cell receptors topologically sample self-ligands during thymocyte β-selection. Science. 2021 Jan 8;371(6525):181-185. PMID:33335016 doi:10.1126/science.abe0918

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