Cryo-EM structure of dodecamer human p97 in complex with NMS-873 reveals S765-G779 peptide plays critical role for D2 ring oligomerization

Liu，Shan1,2,3; Ye，Xuejun3,4; Liu，Wei5; Liu，Li3,4; Li，Dan4,6; Lin，Qihui3; Wang，Tao4,6,7

2022-04-23

10.1016/j.bbrc.2022.02.056

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   影响因子和分区

0006-291X

1090-2104

The AAA + ATPase p97 is a well-known hexametric enzyme that is evolutionary conserved in eukaryotes. p97 contains an amino-terminal N domain, two tandem ATPase domains (D1 and D2 domain) and a C-terminal unstructured extensive tail, involved in many cellular processes and plays important biological functions, but the structural basis of p97 for its biological roles still remain unclear. Here we report the Cryo-EM structure of full-length human p97 dodecamer in 3.0 Å resolution, the structure was captured in ADP-bound form but only D1 ATPase sites were well occupied by nucleotide and D2 sites are empty, furthermore, 12 non-ATP-competitive inhibitors of NMS-873 bound in the interface between each p97 monomer. We also found that the C-terminal S-G (765-‘SRGFGSFRFPSGNQG’-779) peptide plays critical roles for the D2 ring oligomerization, biochemical and electron microscopy studies confirm that the S-G peptide could induce the D2 ring itself to form the heptamer, this give new insights how p97 protomers assemble to the biological functional multimers.

ATPase Cryo-EM NMS-873 Oligomerization p97

SCI

英语

其他

National Key R&D Program of China[2018YFA0507103] ; National Natural Science Foundation of China[31870719] ; National Major Scientific and Technological Special Project of China[2018ZX09711003-003-004] ; Anti-COVID-19 fund of Shenzhen Bay Laboratory[2020B1111340069] ; National Natural Science Youth Fund of China[81901682] ; Shenzhen San-Ming Project[SZSM201809085]

Biochemistry & Molecular Biology ; Biophysics

Biochemistry & Molecular Biology ; Biophysics

WOS:000770867500008

ACADEMIC PRESS INC ELSEVIER SCIENCE

BIOLOGY & BIOCHEMISTRY

2-s2.0-85125480010

Scopus

1.Harbin Institute of Technology,Harbin,Heilongjiang,150001,China
2.Department of Biology,Southern University of Science and Technology,Shenzhen,1088 Xueyuan Road,518055,China
3.Joint Laboratory for Infectious Disease Prevention and Control,Hygienic Section of Longhua Center for Disease Control and Prevention,Shenzhen,Longhua District,518109,China
4.Institute of Infectious Diseases,Shenzhen Bay Laboratory,Shenzhen,Guangming District,518132,China
5.College of Laboratory Medicine,Jilin Medical University,Jilin,132013,China
6.School of Basic Medical Sciences,Capital Medical University,10 Xitoutiao You'anMen Street, Beijing,100069,China
7.Key Laboratory of Computational Chemistry and Drug Design,Peking University Shenzhen Graduate School,Shenzhen,Nanshan District,518055,China

Liu，Shan,Ye，Xuejun,Liu，Wei,et al. Cryo-EM structure of dodecamer human p97 in complex with NMS-873 reveals S765-G779 peptide plays critical role for D2 ring oligomerization[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2022,601:146-152.

Liu，Shan.,Ye，Xuejun.,Liu，Wei.,Liu，Li.,Li，Dan.,...&Wang，Tao.(2022).Cryo-EM structure of dodecamer human p97 in complex with NMS-873 reveals S765-G779 peptide plays critical role for D2 ring oligomerization.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,601,146-152.

Liu，Shan,et al."Cryo-EM structure of dodecamer human p97 in complex with NMS-873 reveals S765-G779 peptide plays critical role for D2 ring oligomerization".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 601(2022):146-152.