9C96
Cryo-EM structure of TAP binding protein related (TAPBPR) in complex with HLA-A*02:01 bound to a suboptimal peptide.
Summary for 9C96
| Entry DOI | 10.2210/pdb9c96/pdb |
| EMDB information | 45360 |
| Descriptor | MHC class I antigen, Beta-2-microglobulin, Tapasin-related protein, ... (4 entities in total) |
| Functional Keywords | antigen processing and presentation, tap binding protein related, mhc-i, chaperone, immune system |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 85726.07 |
| Authors | Pumroy, R.P.,Mallik, L.,Sun, Y.,Moiseenkova-Bell, Y.V.,Sgourakis, N.G. (deposition date: 2024-06-13, release date: 2025-01-22, Last modification date: 2025-01-29) |
| Primary citation | Sun, Y.,Pumroy, R.A.,Mallik, L.,Chaudhuri, A.,Wang, C.,Hwang, D.,Danon, J.N.,Dasteh Goli, K.,Moiseenkova-Bell, V.Y.,Sgourakis, N.G. CryoEM structure of an MHC-I/TAPBPR peptide-bound intermediate reveals the mechanism of antigen proofreading. Proc.Natl.Acad.Sci.USA, 122:e2416992122-e2416992122, 2025 Cited by PubMed Abstract: Class I major histocompatibility complex (MHC-I) proteins play a pivotal role in adaptive immunity by displaying epitopic peptides to CD8+ T cells. The chaperones tapasin and TAPBPR promote the selection of immunogenic antigens from a large pool of intracellular peptides. Interactions of chaperoned MHC-I molecules with incoming peptides are transient in nature, and as a result, the precise antigen proofreading mechanism remains elusive. Here, we leverage a high-fidelity TAPBPR variant and conformationally stabilized MHC-I, to determine the solution structure of the human antigen editing complex bound to a peptide decoy by cryogenic electron microscopy (cryo-EM) at an average resolution of 3.0 Å. Antigen proofreading is mediated by transient interactions formed between the nascent peptide binding groove with the P2/P3 peptide anchors, where conserved MHC-I residues stabilize incoming peptides through backbone-focused contacts. Finally, using our high-fidelity chaperone, we demonstrate robust peptide exchange on the cell surface across multiple clinically relevant human MHC-I allomorphs. Our work has important ramifications for understanding the selection of immunogenic epitopes for T cell screening and vaccine design applications. PubMed: 39786927DOI: 10.1073/pnas.2416992122 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3 Å) |
Structure validation
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