NMR spectroscopy uncovers direct interaction between BAF60A and p53

Jeongmin Han; Taehee Kim; Sunjin Moon; Jae-Hyun Park; Wonbin Lee; Yoon-Joo Ko; Kyoung-Seok Ryu; Ji-Hye Yun; Weontae Lee

doi:10.1016/j.bbrc.2020.10.101

NMR spectroscopy uncovers direct interaction between BAF60A and p53

Biochem Biophys Res Commun. 2021 Jan 1:534:815-821. doi: 10.1016/j.bbrc.2020.10.101. Epub 2020 Nov 7.

Authors

Jeongmin Han¹, Taehee Kim¹, Sunjin Moon¹, Jae-Hyun Park¹, Wonbin Lee¹, Yoon-Joo Ko², Kyoung-Seok Ryu³, Ji-Hye Yun⁴, Weontae Lee⁵

Affiliations

¹ Structural Biochemistry & Molecular Biophysics Laboratory, Department of Biochemistry, College of Life Sciences & Biotechnology, Yonsei University, Seoul, 120-749, South Korea.
² Nuclear Magnetic Resonance Laboratory, National Center for Inter-University Research Facilities, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 151-742, South Korea.
³ Division of Magnetic Resonance Research, Korea Basic Science Institute, Yangcheong-Ri 804-1, Ochang-Eup, Cheongwon-Gun, Chungcheongbuk-Do, 363-883, South Korea.
⁴ Structural Biochemistry & Molecular Biophysics Laboratory, Department of Biochemistry, College of Life Sciences & Biotechnology, Yonsei University, Seoul, 120-749, South Korea. Electronic address: jihye2@spin.yonsei.ac.kr.
⁵ Structural Biochemistry & Molecular Biophysics Laboratory, Department of Biochemistry, College of Life Sciences & Biotechnology, Yonsei University, Seoul, 120-749, South Korea. Electronic address: wlee@spin.yonsei.ac.kr.

PMID: 33168186
DOI: 10.1016/j.bbrc.2020.10.101

Abstract

The BRG1-associated factor 60A (BAF60A), an SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D member 1, has been known to be important for transcriptional activation and inhibition through the alteration of the DNA nucleosome. Although the association between BAF60A and p53 plays a critical role in tumor suppression, the interaction mode is still unclear. Here, we report the detailed interactions between BAF60A and p53 by both NMR spectroscopy and pull-down analysis. Both N-terminal region (BAF60A^NR) and the SWIB domain (BAF60A^SWIB) of BAF60A directly interact with the tetramerization domain of p53 (p53^TET). NMR data show that Ile315, Met366, Ala388, and Tyr390 of BAF60A^SWIB are mostly involved in p53^TET binding. The calculated dissociation constant (K_D) value between BAF60A^SWIB and p53^TET revealed relatively weak binding affinity, at approximately 0.3 ± 0.065 mM. Our data will enhance detailed interaction mechanism to elucidate the molecular basis of p53-mediated integration via BAF60A interaction.

Keywords: BAF60A; NMR; SWItch/Sucrose non-fermentable; Tumor suppressor; p53.

Publication types

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

MeSH terms

Binding Sites
Chromosomal Proteins, Non-Histone / genetics
Chromosomal Proteins, Non-Histone / metabolism*
Humans
Molecular Docking Simulation
Nuclear Magnetic Resonance, Biomolecular / methods
Protein Interaction Domains and Motifs
Protein Interaction Maps
Tumor Suppressor Protein p53 / genetics
Tumor Suppressor Protein p53 / metabolism*

Substances

Chromosomal Proteins, Non-Histone
SMARCD1 protein, human
TP53 protein, human
Tumor Suppressor Protein p53