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

被引:60
作者
Adams-Cioaba, Melanie A. [2 ]
Krupa, Joanne C. [1 ]
Xu, Chao [2 ]
Mort, John S. [1 ,3 ]
Min, Jinrong [2 ,4 ]
机构
[1] Shriners Hosp Children, Genet Unit, Montreal, PQ H3G 1A6, Canada
[2] Univ Toronto, Struct Genom Consortium, Toronto, ON M5G 1L7, Canada
[3] McGill Univ, Dept Surg, Montreal, PQ H3G 1A4, Canada
[4] Univ Toronto, Dept Physiol, Toronto, ON M5S 1A8, Canada
来源
NATURE COMMUNICATIONS | 2011年 / 2卷
基金
英国惠康基金;
关键词
LYSOSOMAL CYSTEINE PROTEASES; CRYSTAL-STRUCTURE; INHIBITOR CHAGASIN; MENT; COMPLEX; HETEROCHROMATIN; SPECIFICITY; PROTEINASE; REFINEMENT; EXPRESSION;
D O I
10.1038/ncomms1204
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页数:8
相关论文
共 39 条
[1]  
Adachi W, 1998, INVEST OPHTH VIS SCI, V39, P1789
[2]   Human cathepsin V functional expression, tissue distribution, electrostatic surface potential, enzymatic characterization, and chromosomal localization [J].
Brömme, D ;
Li, ZQ ;
Barnes, M ;
Mehler, E .
BIOCHEMISTRY, 1999, 38 (08) :2377-2385
[3]   Cathepsin L stabilizes the histone modification landscape on the Y chromosome and pericentromeric heterochromatin [J].
Bulynko, Yaroslava A. ;
Hsing, Lianne C. ;
Mason, Robert W. ;
Tremethick, David J. ;
Grigoryev, Sergei A. .
MOLECULAR AND CELLULAR BIOLOGY, 2006, 26 (11) :4172-4184
[4]   Stefin B Interacts with Histones and Cathepsin L in the Nucleus [J].
Ceru, Slavko ;
Konjar, Spela ;
Maher, Katarina ;
Repnik, Urska ;
Krizaj, Igor ;
Bencina, Mojca ;
Renko, Miha ;
Nepveu, Alain ;
Zerovnik, Eva ;
Turk, Boris ;
Kopitar-Jerala, Natasa .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (13) :10078-10086
[5]   Substrate profiling of cysteine proteases using a combinatorial peptide library identifies functionally unique specificities [J].
Choe, Y ;
Leonetti, F ;
Greenbaum, DC ;
Lecaille, F ;
Bogyo, M ;
Brömme, D ;
Ellman, JA ;
Craik, CS .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (18) :12824-12832
[6]   Design of noncovalent inhibitors of human cathepsin L.: From the 96-residue proregion to optimized tripeptides [J].
Chowdhury, SF ;
Sivaraman, J ;
Wang, J ;
Devanathan, G ;
Lachance, P ;
Qi, HT ;
Ménard, R ;
Lefebvre, J ;
Konishi, Y ;
Cygler, M ;
Sulea, T ;
Purisima, EO .
JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (24) :5321-5329
[7]   Exploring inhibitor binding at the S′ subsites of cathepsin L [J].
Chowdhury, Shafinaz F. ;
Joseph, Lissa ;
Kumar, S. ;
Tulsidas, Shenoy Rajesh ;
Bhat, Sathesh ;
Ziomek, Edmund ;
Menard, Robert ;
Sivaraman, J. ;
Purisima, Enrico O. .
JOURNAL OF MEDICINAL CHEMISTRY, 2008, 51 (05) :1361-1368
[8]   Cathepsin L Proteolytically Processes Histone H3 During Mouse Embryonic Stem Cell Differentiation [J].
Duncan, Elizabeth M. ;
Muratore-Schroeder, Tara L. ;
Cook, Richard G. ;
Garcia, Benjamin A. ;
Shabanowitz, Jeffrey ;
Hunt, Donald F. ;
Allis, C. David .
CELL, 2008, 135 (02) :284-294
[9]   Coot:: model-building tools for molecular graphics [J].
Emsley, P ;
Cowtan, K .
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2004, 60 :2126-2132
[10]   The crystal structure of human cathepsin L complexed with E-64 [J].
Fujishima, A ;
Imai, Y ;
Nomura, T ;
Fujisawa, Y ;
Yamamoto, Y ;
Sugawara, T .
FEBS LETTERS, 1997, 407 (01) :47-50