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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.

SUBMITTER: Adams-Cioaba MA

PROVIDER: S-EPMC3105313 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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Structural basis for the recognition and cleavage of histone H3 by cathepsin L.

Adams-Cioaba Melanie A MA Krupa Joanne C JC Xu Chao C Mort John S JS Min Jinrong J

Nature communications 20110215

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 interac ...[more]

PMID: 21326229

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