Structural insights into multifunctionality of human FACT complex subunit hSSRP1

Xuehui Li; Huiyan Li; Qian Jing; Mengxue Wang; Tingting Hu; Li Li; Qiuping Zhang; Mengxin Liu; Yu Vincent Fu; Junhong Han; Dan Su

doi:10.1016/j.jbc.2021.101360

Structural insights into multifunctionality of human FACT complex subunit hSSRP1

J Biol Chem. 2021 Dec;297(6):101360. doi: 10.1016/j.jbc.2021.101360. Epub 2021 Oct 28.

Authors

Xuehui Li¹, Huiyan Li¹, Qian Jing², Mengxue Wang³, Tingting Hu⁴, Li Li¹, Qiuping Zhang¹, Mengxin Liu¹, Yu Vincent Fu³, Junhong Han⁵, Dan Su⁶

Affiliations

¹ State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan, China.
² Research Laboratory of Tumor Epigenetics and Genomics, Department of General Surgery, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy, and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
³ State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
⁴ College of Life Sciences, Neijiang Normal University, Neijiang, Sichuan, China.
⁵ Research Laboratory of Tumor Epigenetics and Genomics, Department of General Surgery, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy, and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China. Electronic address: [email protected].
⁶ State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan, China; Infectious Disease Drug Discovery Institute, Tianjin International Joint Academy of Biotechnology and Medicine, Tianjin, China. Electronic address: [email protected].

Abstract

Human structure-specific recognition protein 1 (hSSRP1) is an essential component of the facilitates chromatin transcription complex, which participates in nucleosome disassembly and reassembly during gene transcription and DNA replication and repair. Many functions, including nuclear localization, histone chaperone activity, DNA binding, and interaction with cellular proteins, are attributed to hSSRP1, which contains multiple well-defined domains, including four pleckstrin homology (PH) domains and a high-mobility group domain with two flanking disordered regions. However, little is known about the mechanisms by which these domains cooperate to carry out hSSRP1's functions. Here, we report the biochemical characterization and structure of each functional domain of hSSRP1, including the N-terminal PH1, PH2, PH3/4 tandem PH, and DNA-binding high-mobility group domains. Furthermore, two casein kinase II binding sites in hSSRP1 were identified in the PH3/4 domain and in a disordered region (Gly⁶¹⁷-Glu⁷⁰⁹) located in the C-terminus of hSSRP1. In addition, a histone H2A-H2B binding motif and a nuclear localization signal (Lys⁶⁷⁷‒Asp⁶⁸⁷) of hSSRP1 are reported for the first time. Taken together, these studies provide novel insights into the structural basis for hSSRP1 functionality.

Keywords: FACT complex; HMG domain; PH domain; hSSRP1; histone chaperone.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Binding Sites
DNA-Binding Proteins / chemistry
DNA-Binding Proteins / metabolism*
High Mobility Group Proteins / chemistry
High Mobility Group Proteins / metabolism*
Humans
Nuclear Localization Signals
Protein Conformation
Protein Domains
Sequence Homology, Amino Acid
Transcriptional Elongation Factors / chemistry
Transcriptional Elongation Factors / metabolism*

Substances

DNA-Binding Proteins
High Mobility Group Proteins
Nuclear Localization Signals
SSRP1 protein, human
Transcriptional Elongation Factors