7ST3

Consequences of HLA single chain trimer mutations on peptide presentation and binding affinity

This is a non-PDB format compatible entry.

Summary for 7ST3

• Entry DOI: 10.2210/pdb7st3/pdb
• Descriptor: Protein E7 peptide,Beta-2-microglobulin,MHC class I antigen chimera, VHH (3 entities in total)
• Functional Keywords: hla, vhh, sct, hpv, immune system-viral protein complex, immune system/viral protein
• Biological source: Human papillomavirus type 16; More
• Total number of polymer chains: 32
• Total formula weight: 973054.34

Authors

Finton, K.A.K.,Rupert, P.B. (deposition date: 2021-11-11, release date: 2022-11-23, Last modification date: 2024-10-23)

Primary citation

Finton, K.A.K.,Rupert, P.B.,Friend, D.J.,Dinca, A.,Lovelace, E.S.,Buerger, M.,Rusnac, D.V.,Foote-McNabb, U.,Chour, W.,Heath, J.R.,Campbell, J.S.,Pierce, R.H.,Strong, R.K.
Effects of HLA single chain trimer design on peptide presentation and stability.
Front Immunol, 14:1170462-1170462, 2023

PubMed Abstract: MHC class I "" molecules, coupling MHC heavy chain, β-microglobulin, and a specific peptide into a single polypeptide chain, are widely used in research. To more fully understand caveats associated with this design that may affect its use for basic and translational studies, we evaluated a set of engineered single-chain trimers with combinations of stabilizing mutations across eight different classical and non-classical human class I alleles with 44 different peptides, including a novel human/murine chimeric design. While, overall, single-chain trimers accurately recapitulate native molecules, care was needed in selecting designs for studying peptides longer or shorter than 9-mers, as single-chain trimer design could affect peptide conformation. In the process, we observed that of peptide binding were often discordant with and that yields and stabilities varied widely with construct design. We also developed novel reagents to improve the crystallizability of these proteins and confirmed novel modes of peptide presentation.

PubMed: 37207206
DOI: 10.3389/fimmu.2023.1170462

Experimental method

X-RAY DIFFRACTION (2.78 Å)