Cryo-EM structure of the human cohesin-NIPBL-DNA complex

被引:144
作者
Shi, Zhubing [1 ]
Gao, Haishan [1 ]
Bai, Xiao-chen [2 ,3 ]
Yu, Hongtao [1 ,4 ]
机构
[1] Univ Texas Southwestern Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA
[2] Univ Texas Southwestern Med Ctr Dallas, Dept Biophys, Dallas, TX 75390 USA
[3] Univ Texas Southwestern Med Ctr Dallas, Dept Cell Biol, Dallas, TX 75390 USA
[4] Westlake Univ, Sch Life Sci, Hangzhou 310024, Zhejiang, Peoples R China
基金
美国国家卫生研究院;
关键词
SISTER-CHROMATID COHESION; CRYSTAL-STRUCTURE; SMC PROTEINS; ACETYLATION; CONDENSIN; WAPL; RING; VISUALIZATION; ESTABLISHMENT; ORGANIZATION;
D O I
10.1126/science.abb0981
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
As a ring-shaped adenosine triphosphatase (ATPase) machine, cohesin organizes the eukaryotic genome by extruding DNA loops and mediates sister chromatid cohesion by topologically entrapping DNA. How cohesin executes these fundamental DNA transactions is not understood. Using cryo-electron microscopy (cryo-EM), we determined the structure of human cohesin bound to its loader NIPBL and DNA at medium resolution. Cohesin and NIPBL interact extensively and together form a central tunnel to entrap a 72-base pair DNA. NIPBL and DNA promote the engagement of cohesin's ATPase head domains and ATP binding. The hinge domains of cohesin adopt an "open washer" conformation and dock onto the STAG1 subunit. Our structure explains the synergistic activation of cohesin by NIPBL and DNA and provides insight into DNA entrapment by cohesin.
引用
收藏
页码:1454 / +
页数:34
相关论文
共 79 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]   New tools for the analysis and validation of cryo-EM maps and atomic models [J].
Afonine, Pavel V. ;
Klaholz, Bruno P. ;
Moriarty, Nigel W. ;
Poon, Billy K. ;
Sobolev, Oleg V. ;
Terwilliger, Thomas C. ;
Adams, Paul D. ;
Urzhumtsev, Alexandre .
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2018, 74 :814-840
[3]   Real-space refinement in PHENIX for cryo-EM and crystallography [J].
Afonine, Pavel V. ;
Poon, Billy K. ;
Read, Randy J. ;
Sobolev, Oleg V. ;
Terwilliger, Thomas C. ;
Urzhumtsev, Alexandre ;
Adams, Paul D. .
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2018, 74 :531-544
[4]   Towards automated crystallographic structure refinement with phenix.refine [J].
Afonine, Pavel V. ;
Grosse-Kunstleve, Ralf W. ;
Echols, Nathaniel ;
Headd, Jeffrey J. ;
Moriarty, Nigel W. ;
Mustyakimov, Marat ;
Terwilliger, Thomas C. ;
Urzhumtsev, Alexandre ;
Zwart, Peter H. ;
Adams, Paul D. .
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2012, 68 :352-367
[5]   Self-organization of domain structures by DNA-loop-extruding enzymes [J].
Alipour, Elnaz ;
Marko, John F. .
NUCLEIC ACIDS RESEARCH, 2012, 40 (22) :11202-11212
[6]   Specialized interfaces of Smc5/6 control hinge stability and DNA association [J].
Alt, Aaron ;
Dang, Hung Q. ;
Wells, Owen S. ;
Polo, Luis M. ;
Smith, Matt A. ;
McGrego, Grant A. ;
Welte, Thomas ;
Lehmann, Alan R. ;
Pearl, Laurence H. ;
Murray, Johanne M. ;
Oliver, Antony W. .
NATURE COMMUNICATIONS, 2017, 8
[7]   Condensin and cohesin display different arm conformations with characteristic hinge angles [J].
Anderson, DE ;
Losada, A ;
Erickson, HP ;
Hirano, T .
JOURNAL OF CELL BIOLOGY, 2002, 156 (03) :419-424
[8]   Eco1-dependent cohesin acetylation during establishment of sister chromatid cohesion [J].
Ben-Shahar, Tom Rolef ;
Heeger, Sebastian ;
Lehane, Chris ;
East, Philip ;
Flynn, Helen ;
Skehel, Mark ;
Uhlmann, Frank .
SCIENCE, 2008, 321 (5888) :563-566
[9]   Structure of the cohesin loader Scc2 [J].
Chao, William C. H. ;
Murayama, Yasuto ;
Munoz, Sofia ;
Jones, Andrew W. ;
Wade, Benjamin O. ;
Purkiss, Andrew G. ;
Hu, Xiao-Wen ;
Borg, Aaron ;
Snijders, Ambrosius P. ;
Uhlmann, Frank ;
Singleton, Martin R. .
NATURE COMMUNICATIONS, 2017, 8
[10]   Structural Studies Reveal the Functional Modularity of the Scc2-Scc4 Cohesin Loader [J].
Chao, William C. H. ;
Murayama, Yasuto ;
Munoz, Sofia ;
Costa, Alessandro ;
Uhlmann, Frank ;
Singleton, Martin R. .
CELL REPORTS, 2015, 12 (05) :719-725