6GB7

Structure of H-2Db with scoop loop from tapasin

Summary for 6GB7

• Entry DOI: 10.2210/pdb6gb7/pdb
• Descriptor: H-2 class I histocompatibility antigen, D-B alpha chain, Beta-2-microglobulin, PHE-ALA-PRO-GLY-ASN-TYR-PRO, ... (8 entities in total)
• Functional Keywords: mhc, mhc-i, h-2kb, h-2k(b), immune system
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 14
• Total formula weight: 207023.53

Authors

Hafstrand, I.,Sandalova, T.,Achour, A. (deposition date: 2018-04-13, release date: 2019-03-06, Last modification date: 2024-11-06)

Primary citation

Hafstrand, I.,Sayitoglu, E.C.,Apavaloaei, A.,Josey, B.J.,Sun, R.,Han, X.,Pellegrino, S.,Ozkazanc, D.,Potens, R.,Janssen, L.,Nilvebrant, J.,Nygren, P.A.,Sandalova, T.,Springer, S.,Georgoudaki, A.M.,Duru, A.D.,Achour, A.
Successive crystal structure snapshots suggest the basis for MHC class I peptide loading and editing by tapasin.
Proc.Natl.Acad.Sci.USA, 116:5055-5060, 2019

PubMed Abstract: MHC-I epitope presentation to CD8 T cells is directly dependent on peptide loading and selection during antigen processing. However, the exact molecular bases underlying peptide selection and binding by MHC-I remain largely unknown. Within the peptide-loading complex, the peptide editor tapasin is key to the selection of MHC-I-bound peptides. Here, we have determined an ensemble of crystal structures of MHC-I in complex with the peptide exchange-associated dipeptide GL, as well as the tapasin-associated scoop loop, alone or in combination with candidate epitopes. These results combined with mutation analyses allow us to propose a molecular model underlying MHC-I peptide selection by tapasin. The N termini of bound peptides most probably bind first in the N-terminal and middle region of the MHC-I peptide binding cleft, upon which the peptide C termini are tested for their capacity to dislodge the tapasin scoop loop from the F pocket of the MHC-I cleft. Our results also indicate important differences in peptide selection between different MHC-I alleles.

PubMed: 30808808
DOI: 10.1073/pnas.1807656116

Experimental method

X-RAY DIFFRACTION (2.15 Å)