dc.creator | Remesh, Soumya G. | |
dc.creator | Andreatta, Massimo | |
dc.creator | Ying, Ge | |
dc.creator | Kaever, Thomas | |
dc.creator | Nielsen, Morten | |
dc.creator | McMurtrey, Curtis | |
dc.creator | Hildebrand, William | |
dc.creator | Peters, Bjoern | |
dc.creator | Zajonc, Dirk M. | |
dc.date.accessioned | 2018-06-14T17:50:10Z | |
dc.date.available | 2018-06-14T17:50:10Z | |
dc.date.created | 2018-06-14T17:50:10Z | |
dc.date.issued | 2017-03 | |
dc.identifier | Remesh, Soumya G.; Andreatta, Massimo; Ying, Ge; Kaever, Thomas; Nielsen, Morten; et al.; Unconventional peptide presentation by major histocompatibility complex (MHC) class i allele HLA-A∗02:01: Breaking confinement; American Society for Biochemistry and Molecular Biology; Journal of Biological Chemistry (online); 292; 13; 3-2017; 5262-5270 | |
dc.identifier | 0021-9258 | |
dc.identifier | http://hdl.handle.net/11336/48677 | |
dc.identifier | CONICET Digital | |
dc.identifier | CONICET | |
dc.description.abstract | Peptide antigen presentation by major histocompatibility complex (MHC) class I proteins initiates CD8+ T cell-mediated immunity against pathogens and cancers.MHCI molecules typically bind peptides with 9 amino acids in length with both ends tucked inside the major A and F binding pockets. It has been known for a while that longer peptides can also bind by either bulging out of the groove in the middle of the peptide or by binding in a zigzag fashion inside the groove. In a recent study, we identified an alternative binding conformation of naturally occurring peptides from Toxoplasma gondii bound by HLAA∗ 02:01. These peptides were extended at the C terminus (PΩ) and contained charged amino acids not more than 3 residues after the anchor amino acid at PΩ, which enabled them to open the F pocket and expose their C-terminal extension into the solvent. Here, we show that the mechanism of F pocket opening is dictated by the charge of the first charged amino acid found within the extension. Although positively charged amino acids result in the Tyr-84 swing, amino acids that are negatively charged induce a not previously described Lys-146 lift. Furthermore, we demonstrate that the peptides with alternative binding modes have properties that fit very poorly to the conventional MHC class I pathway and suggest they are presented via alternative means, potentially including cross-presentation via the MHC class II pathway. | |
dc.language | eng | |
dc.publisher | American Society for Biochemistry and Molecular Biology | |
dc.relation | info:eu-repo/semantics/altIdentifier/doi/https://dx.doi.org/10.1074/jbc.M117.776542 | |
dc.relation | info:eu-repo/semantics/altIdentifier/url/http://www.jbc.org/content/292/13/5262 | |
dc.rights | https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ | |
dc.rights | info:eu-repo/semantics/openAccess | |
dc.subject | Mhc | |
dc.subject | Toxoplasma Gondii | |
dc.subject | Mass Spec | |
dc.title | Unconventional peptide presentation by major histocompatibility complex (MHC) class i allele HLA-A∗02:01: Breaking confinement | |
dc.type | info:eu-repo/semantics/article | |
dc.type | info:ar-repo/semantics/artículo | |
dc.type | info:eu-repo/semantics/publishedVersion | |