Structure and function of a HECT domain ubiquitin-binding site

被引:100
作者
Kim, Hyung Cheol [1 ]
Steffen, Alanna M. [2 ]
Oldham, Michael L. [2 ]
Chen, Jue [2 ]
Huibregtse, Jonm. [1 ]
机构
[1] Univ Texas Austin, Inst Cellular & Mol Biol, Austin, TX 78712 USA
[2] Purdue Univ, Howard Hughes Med Inst, Dept Biol Sci, W Lafayette, IN 47907 USA
基金
美国国家卫生研究院;
关键词
HECT; polyubiquitin chains; Rsp5; ubiquitin; COMPLEX; LIGASE; DETERMINANTS; SOFTWARE; INSIGHTS; CASCADE; RSP5; E2;
D O I
10.1038/embor.2011.23
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The Rsp5 ubiquitin ligase contains a non-covalent binding site for ubiquitin within the amino-terminal lobe (N-lobe) of the HECT domain, and the X-ray crystal structure of the HECT-ubiquitin complex has been determined. Hydrophobic patch residues of ubiquitin (L8, I44, V70) were crucial for interaction with Rsp5, and amino-acid alterations at the Rsp5-binding interface resulted in defects in polyubiquitination. Our results support a model in which the N-lobe-binding site acts to localize and orient the distal end of the ubiquitin chain to promote conjugation of the next ubiquitin molecule.
引用
收藏
页码:334 / 341
页数:8
相关论文
共 20 条
[1]   A robust bulk-solvent correction and anisotropic scaling procedure [J].
Afonine, PV ;
Grosse-Kunstleve, RW ;
Adams, PD .
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 2005, 61 :850-855
[2]   Crystallography & NMR system:: A new software suite for macromolecular structure determination [J].
Brunger, AT ;
Adams, PD ;
Clore, GM ;
DeLano, WL ;
Gros, P ;
Grosse-Kunstleve, RW ;
Jiang, JS ;
Kuszewski, J ;
Nilges, M ;
Pannu, NS ;
Read, RJ ;
Rice, LM ;
Simonson, T ;
Warren, GL .
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1998, 54 :905-921
[3]   Ubiquitin-binding domains - from structures to functions [J].
Dikic, Ivan ;
Wakatsuki, Soichi ;
Walters, Kylie J. .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2009, 10 (10) :659-671
[4]   E2 conjugating enzymes must disengage from their E1 enzymes before E3-dependent ubiquitin and ubiquitin-like transfer [J].
Eletr, ZM ;
Huang, DT ;
Duda, DM ;
Schulman, BA ;
Kuhlman, B .
NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2005, 12 (10) :933-934
[5]   Coot:: model-building tools for molecular graphics [J].
Emsley, P ;
Cowtan, K .
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2004, 60 :2126-2132
[6]   Regulation of the RSP5 Ubiquitin Ligase by an Intrinsic Ubiquitin-binding Site [J].
French, Michael E. ;
Kretzmann, Benjamin R. ;
Hicke, Linda .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (18) :12071-12079
[7]   Structure of an E6AP-UbcH7 complex: Insights into ubiquitination by the E2-E3 enzyme cascade [J].
Huang, L ;
Kinnucan, E ;
Wang, GL ;
Beaudenon, S ;
Howley, PM ;
Huibregtse, JM ;
Pavletich, NP .
SCIENCE, 1999, 286 (5443) :1321-1326
[8]   Insights into Ubiauitin Transfer Cascades from a Structure of a UbcH5B∼Ubiauitin-HECTNEDD4L Complex [J].
Kamadurai, Hari B. ;
Souphron, Judith ;
Scott, Daniel C. ;
Duda, David M. ;
Miller, Darcie J. ;
Stringer, Daniel ;
Piper, Robert C. ;
Schulman, Brenda A. .
MOLECULAR CELL, 2009, 36 (06) :1095-1102
[9]   Polyubiquitination by HECT E3s and the Determinants of Chain Type Specificity [J].
Kim, Hyung Cheol ;
Huibregtse, Jon M. .
MOLECULAR AND CELLULAR BIOLOGY, 2009, 29 (12) :3307-3318
[10]   Structure of the HECT:ubiquitin complex and its role in ubiquitin chain elongation [J].
Maspero, Elena ;
Mari, Sara ;
Valentini, Eleonora ;
Musacchio, Andrea ;
Fish, Alexander ;
Pasqualato, Sebastiano ;
Polo, Simona .
EMBO REPORTS, 2011, 12 (04) :342-349