Successive crystal structure snapshots suggest the basis for MHC class i peptide loading and editing by tapasin

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.; Sandalova, T.; Springer, S.; Georgoudaki, A.; Duru, A.D.; Achour, A.

doi:10.1073/pnas.1807656116

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
Autori:	Hafstrand, Ida Sayitoglu, Ece Canan Apavaloaei, Anca Josey, Benjamin John Sun, Renhua Han, Xiao PELLEGRINO, SARA Ozkazanc, Didem Potens, Renée Janssen, Linda Nilvebrant, Johan Nygren, Per-Åke Sandalova, Tatyana Springer, Sebastian Georgoudaki, Anna-Maria Duru, Adil Doganay Achour, Adnane mostra contributor esterni nascondi contributor esterni
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
Rivista:	PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Tipologia:	Article (author)
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

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