title: Crystal structure of a nuclear actin ternary complex.
abstract: Actin polymerizes and forms filamentous structures (F-actin) in the cytoplasm of eukaryotic cells. It also exists in the nucleus and regulates various nucleic acid transactions, particularly through its incorporation into multiple chromatin-remodeling complexes. However, the specific structure of actin and the mechanisms that regulate its polymeric nature inside the nucleus remain unknown. Here, we report the crystal structure of nuclear actin (N-actin) complexed with actin-related protein 4 (Arp4) and the helicase-SANT-associated (HSA) domain of the chromatin remodeler Swr1. The inner face and barbed end of N-actin are sequestered by interactions with Arp4 and the HSA domain, respectively, which prevents N-actin from polymerization and binding to many actin regulators. The two major domains of N-actin are more twisted than those of globular actin (G-actin), and its nucleotide-binding pocket is occluded, freeing N-actin from binding to and regulation by ATP. These findings revealed the salient structural features of N-actin that distinguish it from its cytoplasmic counterpart and provide a rational basis for its functions and regulation inside the nucleus.
authors.affiliation: Ministry of Education Key Laboratory of Protein Science, Tsinghua University, Beijing 100084, P.R. China; School of Life Science, Tsinghua University, Beijing 100084, P.R. China;
authors.forename: Tingting
authors.initials: T
authors.lastname: Cao
authors.affiliation: Ministry of Education Key Laboratory of Protein Science, Tsinghua University, Beijing 100084, P.R. China; School of Life Science, Tsinghua University, Beijing 100084, P.R. China;
authors.forename: Lingfei
authors.initials: L
authors.lastname: Sun
authors.affiliation: School of Life Science, Tsinghua University, Beijing 100084, P.R. China;
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: School of Life Science, Tsinghua University, Beijing 100084, P.R. China;
authors.forename: Shanjin
authors.initials: S
authors.lastname: Huang
authors.affiliation: School of Life Science, Tsinghua University, Beijing 100084, P.R. China; State Key Laboratory of Bio-membrane and Membrane Biotechnology, Tsinghua University, Beijing 100086, P.R. China.
authors.forename: Jiawei
authors.initials: J
authors.lastname: Wang
authors.affiliation: Ministry of Education Key Laboratory of Protein Science, Tsinghua University, Beijing 100084, P.R. China; School of Life Science, Tsinghua University, Beijing 100084, P.R. China; zhucheng_chen@tsinghua.edu.cn.
authors.forename: Zhucheng
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000199:Actins / Q000737:chemistry*; D000255:Adenosine Triphosphate / Q000737:chemistry; D002467:Cell Nucleus / Q000737:chemistry*; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry*; D003460:Crystallization; D004268:DNA-Binding Proteins / Q000737:chemistry*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D000072417:Protein Domains
chemical_list: C116160:ACTL6A protein, human; D000199:Actins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D000255:Adenosine Triphosphate
keywords: Arp4; chromatin remodeling; crystal structure; nuclear actin