Quasi-Racemic X-ray Structures of K27-Linked Ubiquitin Chains Prepared by Total Chemical Synthesis

被引：208

作者：

Pan, Man ^{[1
]}

Gao, Shuai ^{[1
]}

Zheng, Yong ^{[1
]}

Tan, Xiaodan ^{[1
]}

Lan, Huan ^{[1
]}

Tan, Xianglong ^{[1
]}

Sun, Demeng ^{[1
]}

Lu, Lining ^{[1
]}

Wang, Tian ^{[1
]}

Zheng, Qingyun ^{[1
]}

Huang, Yichao ^{[1
]}

Wang, Jiawei ^{[2
]}

Liu, Lei ^{[1
]}

机构：

[1] Tsinghua Univ, Dept Chem, Tsinghua Peking Ctr Life Sci, Minist Educ,Key Lab Bioorgan Phosphorus Chem & Ch, Beijing 100084, Peoples R China

[2] Tsinghua Univ, Sch Life Sci, Struct Biol Ctr, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100084, Peoples R China

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2016年 / 138卷 / 23期

关键词：

DIFFRACTION DATA; PROTEIN; POLYUBIQUITIN; THIOESTER; SPECIFICITY; HYDRAZIDE; LIGATION; CYSTEINE; CRYSTALS; ENZYMES;

D O I：

10.1021/jacs.6b04031

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Quasi-racemic crystallography has been used to determine the X-ray structures of K27-linked ubiquitin (Ub) chains prepared through total chemical synthesis. Crystal structures of 1(27 linked di- and tri-ubiquitins reveal that the isopeptide linkages are confined in a unique buried conformation, which provides the molecular basis for the distinctive function of K27 linkage compared to the other seven Ub chains. K27-linked di- and triUb were found to adopt different structural conformations in the crystals, one being symmetric whereas the other triangular. Furthermore, bioactivity experiments showed that the ovarian tumor family de-ubiquitinase 2 significantly favors K27-linked triUb than K27-linked diUb. K27-linked triUb represents the so-far largest chemically synthesized protein (228 amino acids) that has been crystallized to afford a high-resolution X-ray structure.

引用

页码：7429 / 7435

页数：7

共 69 条

[1] PHENIX: a comprehensive Python']Python-based system for macromolecular structure solution [J].

Adams, Paul D. ;

Afonine, Pavel V. ;

Bunkoczi, Gabor ;

Chen, Vincent B. ;

Davis, Ian W. ;

Echols, Nathaniel ;

Headd, Jeffrey J. ;

Hung, Li-Wei ;

Kapral, Gary J. ;

Grosse-Kunstleve, Ralf W. ;

McCoy, Airlie J. ;

Moriarty, Nigel W. ;

Oeffner, Robert ;

Read, Randy J. ;

Richardson, David C. ;

Richardson, Jane S. ;

Terwilliger, Thomas C. ;

Zwart, Peter H. .

ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2010, 66 :213-221

[2] PHENIX:: building new software for automated crystallographic structure determination [J].

Adams, PD ;

Grosse-Kunstleve, RW ;

Hung, LW ;

Ioerger, TR ;

McCoy, AJ ;

Moriarty, NW ;

Read, RJ ;

Sacchettini, JC ;

Sauter, NK ;

Terwilliger, TC .

ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2002, 58 :1948-1954

[3] The Ball and Chain of Polyubiquitin Structures [J].

Alfano, Caterina ;

Faggiano, Serena ;

Pastore, Annalisa .

TRENDS IN BIOCHEMICAL SCIENCES, 2016, 41 (04) :371-385

[4] Fully Convergent Chemical Synthesis of Ester Insulin: Determination of the High Resolution X-ray Structure by Racemic Protein Crystallography [J].

Avital-Shmilovici, Michal ;

Mandal, Kalyaneswar ;

Gates, Zachary P. ;

Phillips, Nelson B. ;

Weiss, Michael A. ;

Kent, Stephen B. H. .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2013, 135 (08) :3173-3185

[5] THE CCP4 SUITE - PROGRAMS FOR PROTEIN CRYSTALLOGRAPHY [J].

BAILEY, S .

ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1994, 50 :760-763

[6] Lys11-linked ubiquitin chains adopt compact conformations and are preferentially hydrolyzed by the deubiquitinase Cezanne [J].

Bremm, Anja ;

Freund, Stefan M. V. ;

Komander, David .

NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2010, 17 (08) :939-U47

[7] A functional role of Rv1738 in Mycobacterium tuberculosis persistence suggested by racemic protein crystallography [J].

Bunker, Richard D. ;

Mandal, Kalyaneswar ;

Bashiri, Ghader ;

Chaston, Jessica J. ;

Pentelute, Bradley L. ;

Lott, J. Shaun ;

Kent, Stephen B. H. ;

Baker, Edward N. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2015, 112 (14) :4310-4315

[8] Nonenzymatic Assembly of Natural Polyubiquitin Chains of Any Linkage Composition and Isotopic Labeling Scheme [J].

Castaneda, Carlos ;

Liu, Jia ;

Chaturvedi, Apurva ;

Nowicka, Urszula ;

Cropp, T. Ashton ;

Fushman, David .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2011, 133 (44) :17855-17868

[9] Linkage via K27 Bestows Ubiquitin Chains with Unique Properties among Polyubiquitins [J].

Castaneda, Carlos A. ;

Dixon, Emma K. ;

Walker, Olivier ;

Chaturvedi, Apurva ;

Nakasone, Mark A. ;

Curtis, Joseph E. ;

Reed, Megan R. ;

Krueger, Susan ;

Cropp, T. Ashton ;

Fushman, David .

STRUCTURE, 2016, 24 (03) :423-436

[10] Linkage-specific conformational ensembles of non-canonical polyubiquitin chains [J].

Castaneda, Carlos A. ;

Chaturvedi, Apurva ;

Camara, Christina M. ;

Curtis, Joseph E. ;

Krueger, Susan ;

Fushman, David .

PHYSICAL CHEMISTRY CHEMICAL PHYSICS, 2016, 18 (08) :5771-5788

← 1 2 3 4 5 6 7 →