9HY4

Solubly expressed miniaturized SMART H2-Db

Summary for 9HY4

• Entry DOI: 10.2210/pdb9hy4/pdb
• Descriptor: H-2 class I histocompatibility antigen, D-B alpha chain, LYS-ALA-VAL-TYR-ASN-PHE-ALA-THR-MET (3 entities in total)
• Functional Keywords: mhc, soluble expression, immune system
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 4
• Total formula weight: 60216.44

Authors

Sun, R.,White, W.,Bai, H.,Baker, D.,Achour, A. (deposition date: 2025-01-09, release date: 2025-12-31, Last modification date: 2026-01-14)

Primary citation

White, W.L.,Bai, H.,Kim, C.J.,Jude, K.M.,Sun, R.,Guerrero, L.,Han, X.,Chen, X.,Chaudhuri, A.,Bonzanini, J.E.,Sun, Y.,Onwuka, A.E.,Wang, N.,Wang, C.,Nygren, P.A.,Li, X.,Goreshnik, I.,Allen, A.,Levine, P.M.,Kueh, H.Y.,Jewett, M.C.,Sgourakis, N.G.,Achour, A.,Garcia, K.C.,Baker, D.
Design of solubly expressed miniaturized SMART MHCs.
Proc.Natl.Acad.Sci.USA, 123:e2505932123-e2505932123, 2026

PubMed Abstract: The precise recognition of specific peptide-major histocompatibility complex (pMHC) complexes by T cell receptors (TCRs) plays a key role in infectious disease, cancer, and autoimmunity. A critical step in many immunobiological studies is the identification of T cells expressing TCRs specific to a given pMHC antigen. However, the intrinsic instability of empty class-I MHCs limits their soluble expression in and makes it very difficult to characterize even a small fraction of possible pMHC/TCR interactions. To overcome this limitation, we designed small proteins which buttress the peptide binding groove of class I MHCs, replacing β2-microglobulin (β2m) and the heavy chain α3 domain, and enable soluble and partially soluble expression in of H-2D and A*02:01, respectively. We demonstrate that these soluble, monomeric, antigen-receptive, truncated (SMART) MHCs retain both peptide- and TCR-binding specificity and that peptide-bound structures of both allomorphs are similar to their full-length, native counterparts. With extension to the majority of HLA alleles, SMART MHCs should be broadly useful for probing the T cell repertoire in approaches ranging from yeast display to T cell staining.

PubMed: 41481462
DOI: 10.1073/pnas.2505932123

Experimental method

X-RAY DIFFRACTION (2 Å)