@article { WOS:000085192500015,
	title = {Sequence signals for generation of antigenic peptides by the proteasome: Implications for proteasomal cleavage mechanism},
	journal = {JOURNAL OF MOLECULAR BIOLOGY},
	volume = {295},
	number = {4},
	year = {2000},
	month = {JAN 28},
	pages = {879-890},
	publisher = {ACADEMIC PRESS LTD},
	type = {Article},
	address = {24-28 OVAL RD, LONDON NW1 7DX, ENGLAND},
	abstract = {Proteasomal cleavage of proteins is the first step in the processing of most antigenic peptides that are presented to cytotoxic T cells. Still, its specificity and mechanism are not fully understood. To identify preferred sequence signals that are used for generation of antigenic peptides by the proteasome, we performed a rigorous analysis of the residues at the termini and flanking regions of naturally processed peptides eluted from MHC class I molecules. Our results show that both the C terminus (position P1 of the cleavage site) and its immediate flanking position (P1{\textquoteright}) possess significant signals. The N termini of the peptides show these signals only weakly, consistent with previous findings that antigenic peptides may be cleaved by the proteasome with N-terminal extensions. Nevertheless, we succeed to demonstrate indirectly that the N-terminal cleavage sites contain the same preferred signals at position P1{\textquoteright}. This reinforces previous findings regarding the role of the P1{\textquoteright} position of a cleavage site in determining the cleavage specificity, in addition to the well-known contribution of position P1. Our results apply to the generation of antigenic peptides and bare direct implications for the mechanism of proteasomal cleavage. We propose a model for proteasomal cleavage mechanism by which both ends of cleaved fragments are determined by the same cleavage signals, involving preferred residues at both P1 and P1{\textquoteright} positions of a cleavage site. The compatibility of this model with experimental data on protein degradation products and generation of antigenic peptides is demonstrated. (C) 2000 Academic Press.},
	keywords = {antigenic peptides, bioinformatics, cleavage, proteasome, sequence signals},
	issn = {0022-2836},
	doi = {10.1006/jmbi.1999.3392},
	url = {https://doi.org/10.1006/jmbi.1999.3392},
	author = {Altuvia, Y and Margalit, H}
}
