Crystal structure and solution NMR studies of Lys48-linked tetraubiquitin at neutral pH

被引:138
作者
Eddins, Michael J.
Varadan, Ranjani
Flushman, David
Pickart, Cecile M.
Wolberger, Cynthia [1 ]
机构
[1] Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA
[2] Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA
[3] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA
[4] Univ Maryland, Ctr Biomol Struct & Org, College Pk, MD 20742 USA
[5] Johns Hopkins Univ, Bloomberg Sch Publ hlth, Dept Biochem & Mol Biol, Baltimore, MD 21205 USA
关键词
ubiquitin; polyubiquitin chains; tetraubiquitin; Lys48-linked; crystal structure;
D O I
10.1016/j.jmb.2006.12.065
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
Ubiquitin modification of proteins is used as a signal in many cellular processes. Lysine side-chains can be modified by a single ubiquitin or by a polyubiquitin chain, which is defined by an isopeptide bond between the C terminus of one ubiquitin and a specific lysine in a neighboring ubiquitin. Polyubiquitin conformations that result from different lysine linkages presumably differentiate their roles and ability to bind specific targets and enzymes. However, conflicting results have been obtained regarding the precise conformation of Lys48-linked tetraubiquitin. We report the crystal structure of Lys48-linked tetraubiquitin at near-neutral pH. The two tetraubiquitin complexes in the asymmetric unit show the complete connectivity of the chain and the molecular details of the interactions. This tetraubiquitin conformation is consistent with our NMR data as well as with previous studies of diubiquitin and tetraubiquitin in solution at neutral pH. The structure provides a basis for understanding Lys48-linked polyubiquitin recognition under physiological conditions. (c) 2007 Elsevier Ltd. All rights reserved.
引用
收藏
页码:204 / 211
页数:8
相关论文
共 32 条
[1]   Surface hydrophobic residues of multiubiquitin chains essential for proteolytic targeting [J].
Beal, R ;
Deveraux, Q ;
Xia, G ;
Rechsteiner, M ;
Pickart, C .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (02) :861-866
[2]   The hydrophobic effect contributes to polyubiquitin chain recognition [J].
Beal, RE ;
Toscano-Cantaffa, D ;
Young, P ;
Rechsteiner, M ;
Pickart, CM .
BIOCHEMISTRY, 1998, 37 (09) :2925-2934
[3]   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
[4]   Ubiquitin signalling in the NF-κB pathway [J].
Chen, ZJJ .
NATURE CELL BIOLOGY, 2005, 7 (08) :758-U19
[5]   STRUCTURE OF TETRAUBIQUITIN SHOWS HOW MULTIUBIQUITIN CHAINS CAN BE FORMED [J].
COOK, WJ ;
JEFFREY, LC ;
KASPEREK, E ;
PICKART, CM .
JOURNAL OF MOLECULAR BIOLOGY, 1994, 236 (02) :601-609
[6]  
COOK WJ, 1992, J BIOL CHEM, V267, P16467
[7]   HYDRONMR: Prediction of NMR relaxation of globular proteins from atomic-level structures and hydrodynamic calculations [J].
de la Torre, JG ;
Huertas, ML ;
Carrasco, B .
JOURNAL OF MAGNETIC RESONANCE, 2000, 147 (01) :138-146
[8]  
DICKINSON B, 2007, IN PRESS PROTEIN SCI
[9]   Ubiquitin-binding domains [J].
Hicke, L ;
Schubert, HL ;
Hill, CP .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2005, 6 (08) :610-621
[10]   IMPROVED METHODS FOR BUILDING PROTEIN MODELS IN ELECTRON-DENSITY MAPS AND THE LOCATION OF ERRORS IN THESE MODELS [J].
JONES, TA ;
ZOU, JY ;
COWAN, SW ;
KJELDGAARD, M .
ACTA CRYSTALLOGRAPHICA SECTION A, 1991, 47 :110-119