title: Structural basis for the recognition and cleavage of histone H3 by cathepsin L.
abstract: Proteolysis of eukaryotic histone tails has emerged as an important factor in the modulation of cell-cycle progression and cellular differentiation. The recruitment of lysosomal cathepsin L to the nucleus where it mediates proteolysis of the mouse histone H3 tail has been described recently. Here, we report the three-dimensional crystal structures of a mature, inactive mutant of human cathepsin L alone and in complex with a peptide derived from histone H3. Canonical substrate-cathepsin L interactions are observed in the complex between the protease and the histone H3 peptide. Systematic analysis of the impact of posttranslational modifications at histone H3 on substrate selectivity suggests cathepsin L to be highly accommodating of all modified peptides. This is the first report of cathepsin L-histone H3 interaction and the first structural description of cathepsin L in complex with a substrate.
authors.affiliation: Structural Genomics Consortium, University of Toronto, 101 College Street, Toronto, Ontario M5G 1L7, Canada.
authors.forename: Melanie A
authors.initials: MA
authors.lastname: Adams-Cioaba
authors.forename: Joanne C
authors.initials: JC
authors.lastname: Krupa
authors.forename: Chao
authors.initials: C
authors.lastname: Xu
authors.forename: John S
authors.initials: JS
authors.lastname: Mort
authors.forename: Jinrong
authors.initials: J
authors.lastname: Min
mesh_terms: D000818:Animals; D056668:Cathepsin L / Q000737:chemistry* / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D003460:Crystallization; D006657:Histones / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D051379:Mice; D008958:Models, Molecular; D010447:Peptide Hydrolases / Q000378:metabolism; D011485:Protein Binding
chemical_list: D006657:Histones; D010447:Peptide Hydrolases; C534281:CTSL protein, human; D056668:Cathepsin L