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 peptideloading 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.
Successive crystal structure snapshots suggest the basis for MHC class i peptide loading and editing by tapasin / I. Hafstrand, E.C. Sayitoglu, A. Apavaloaei, B.J. Josey, R. Sun, X. Han, S. Pellegrino, D. Ozkazanc, R. Potens, L. Janssen, J. Nilvebrant, P. Nygren, T. Sandalova, S. Springer, A. Georgoudaki, A.D. Duru, A. Achour. - In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - ISSN 0027-8424. - 116:11(2019 Mar 12), pp. 5055-5060.
|Titolo:||Successive crystal structure snapshots suggest the basis for MHC class i peptide loading and editing by tapasin|
|Parole Chiave:||MHC-I; Peptide editing; Tapasin; TAPBPR; Multidisciplinary|
|Settore Scientifico Disciplinare:||Settore CHIM/06 - Chimica Organica|
Settore BIO/10 - Biochimica
|Data di pubblicazione:||12-mar-2019|
|Data ahead of print / Data di stampa:||26-feb-2019|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1073/pnas.1807656116|
|Appare nelle tipologie:||01 - Articolo su periodico|