Spindlin-1 recognizes methylations of K20 and R23 of histone H4 tail

Chengliang Wang; Li Zhan; Minhao Wu; Rongsheng Ma; Jun Yao; Ying Xiong; Yang Pan; Shenheng Guan; Xuan Zhang; Jianye Zang

doi:10.1002/1873-3468.13281

Spindlin-1 recognizes methylations of K20 and R23 of histone H4 tail

FEBS Lett. 2018 Dec;592(24):4098-4110. doi: 10.1002/1873-3468.13281. Epub 2018 Nov 17.

Authors

Chengliang Wang^{1

2}, Li Zhan^{1

2}, Minhao Wu^{1

2}, Rongsheng Ma², Jun Yao³, Ying Xiong^{1

2}, Yang Pan⁴, Shenheng Guan⁵, Xuan Zhang^{1

2}, Jianye Zang^{1

2}

Affiliations

¹ Hefei National Laboratory for Physical Sciences at Microscale CAS Center for Excellence in Biomacromolecules, Collaborative Innovation Center of Chemistry for Life Sciences and School of Life Sciences, University of Science and Technology of China, Hefei, China.
² Key Laboratory of Structural Biology, Chinese Academy of Sciences, Hefei, China.
³ Department of Chemistry and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
⁴ National Synchrotron Radiation Laboratory, University of Science and Technology of China, Hefei, China.
⁵ Department of Pharmaceutical Chemistry, University of California, San Francisco, CA, USA.

PMID: 30381828
DOI: 10.1002/1873-3468.13281

Abstract

Using methods combining cross-linking, pull-down assays, and stable isotope labeling by amino acids in cell culture with mass spectrometry, we identified that the Tudor domain-containing protein Spindlin-1 recognizes trimethylation of histone H4 lysine 20 (H4K20me3). The binding affinity of Spindlin-1 to H4K20me3 is weaker than that to H3K4me3, indicating H4K20me3 as a secondary substrate for Spindlin-1. Structural studies of Spindlin-1 in complex with the H4K20me3 peptide indicate that Spindlin-1 attains a distinct binding mode for H4K20me3 recognition. Further biochemical analysis identified that Spindlin-1 also binds methylated R23 of H4, providing new clues for the function of Spindlin-1.

Keywords: H4K20; H4R23; crystal structure; histone methylation; molecular mechanism; spindlin-1.

Publication types

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

MeSH terms

Arginine / chemistry
Arginine / metabolism
Cell Cycle Proteins / chemistry
Cell Cycle Proteins / genetics
Cell Cycle Proteins / metabolism*
Crystallography, X-Ray
HeLa Cells
Histones / chemistry
Histones / metabolism*
Humans
Lysine / chemistry
Lysine / metabolism
Methylation
Microtubule-Associated Proteins / chemistry
Microtubule-Associated Proteins / genetics
Microtubule-Associated Proteins / metabolism*
Models, Molecular
Mutation
Phosphoproteins / chemistry
Phosphoproteins / genetics
Phosphoproteins / metabolism*
Protein Binding
Protein Domains

Substances

Cell Cycle Proteins
Histones
Microtubule-Associated Proteins
Phosphoproteins
spindlin
Arginine
Lysine