9O5S

minibinder-antigen complex BXMart1-3-MART1-HLA*A02

Summary for 9O5S

• Entry DOI: 10.2210/pdb9o5s/pdb
• Descriptor: HLA class I histocompatibility antigen, A alpha chain, Beta-2-microglobulin, Melanoma antigen recognized by T-cells 1, ... (7 entities in total)
• Functional Keywords: minibinder, pmhc, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 20
• Total formula weight: 282962.83

Authors

Xiang, X.,Jude, K.M.,Garcia, K.C. (deposition date: 2025-04-10, release date: 2025-07-23, Last modification date: 2025-08-06)

Primary citation

Liu, B.,Greenwood, N.F.,Bonzanini, J.E.,Motmaen, A.,Meyerberg, J.,Dao, T.,Xiang, X.,Ault, R.,Sharp, J.,Wang, C.,Visani, G.M.,Vafeados, D.K.,Roullier, N.,Nourmohammad, A.,Scheinberg, D.A.,Garcia, K.C.,Baker, D.
Design of high-specificity binders for peptide-MHC-I complexes.
Science, 389:386-391, 2025

PubMed Abstract: Class I major histocompatibility complex (MHC-I) molecules present peptides derived from intracellular antigens on the cell surface for immune surveillance. Proteins that recognize peptide-MHC-I (pMHCI) complexes with specificity for diseased cells could have considerable therapeutic utility. Specificity requires recognition of outward-facing amino acid residues within the disease-associated peptide as well as avoidance of extensive contacts with ubiquitously expressed MHC. We used RFdiffusion to design pMHCI-binding proteins that make extensive contacts with the peptide and identified specific binders for 11 target pMHCs starting from either experimental or predicted pMHCI structures. Upon incorporation into chimeric antigen receptors, designs for eight targets conferred peptide-specific T cell activation. Our approach should have broad utility for both protein- and cell-based pMHCI targeting.

PubMed: 40705892
DOI: 10.1126/science.adv0185

Experimental method

X-RAY DIFFRACTION (2.27 Å)