7PHR

Structure of a fully assembled T-cell receptor engaging a tumor-associated peptide-MHC I

Summary for 7PHR

• Entry DOI: 10.2210/pdb7phr/pdb
• EMDB information: 13427
• Descriptor: T-cell receptor alpha chain, 2-acetamido-2-deoxy-beta-D-glucopyranose, T-cell receptor beta chain, ... (10 entities in total)
• Functional Keywords: t-cell receptor, tcr, major histocompatibility complex, mhc, antigen, adaptive immunity, cancer, complex, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 11
• Total formula weight: 202502.78

Authors

Susac, L.,Thomas, C.,Tampe, R. (deposition date: 2021-08-18, release date: 2022-08-31, Last modification date: 2024-11-13)

Primary citation

Susac, L.,Vuong, M.T.,Thomas, C.,von Bulow, S.,O'Brien-Ball, C.,Santos, A.M.,Fernandes, R.A.,Hummer, G.,Tampe, R.,Davis, S.J.
Structure of a fully assembled tumor-specific T cell receptor ligated by pMHC.
Cell, 185:3201-3213.e19, 2022

PubMed Abstract: The T cell receptor (TCR) expressed by T lymphocytes initiates protective immune responses to pathogens and tumors. To explore the structural basis of how TCR signaling is initiated when the receptor binds to peptide-loaded major histocompatibility complex (pMHC) molecules, we used cryogenic electron microscopy to determine the structure of a tumor-reactive TCRαβ/CD3δγεζ complex bound to a melanoma-specific human class I pMHC at 3.08 Å resolution. The antigen-bound complex comprises 11 subunits stabilized by multivalent interactions across three structural layers, with clustered membrane-proximal cystines stabilizing the CD3-εδ and CD3-εγ heterodimers. Extra density sandwiched between transmembrane helices reveals the involvement of sterol lipids in TCR assembly. The geometry of the pMHC/TCR complex suggests that efficient TCR scanning of pMHC requires accurate pre-positioning of T cell and antigen-presenting cell membranes. Comparisons of the ligand-bound and unliganded receptors, along with molecular dynamics simulations, indicate that TCRs can be triggered in the absence of spontaneous structural rearrangements.

PubMed: 35985289
DOI: 10.1016/j.cell.2022.07.010

Experimental method

ELECTRON MICROSCOPY (3.08 Å)