Structural Insights into ceNAP1 Chaperoning Activity toward ceH2A-H2B

Yongrui Liu; Li Xu; Changlin Xie; Jingjun Hong; Fudong Li; Ke Ruan; Jiajing Chen; Jihui Wu; Yunyu Shi

doi:10.1016/j.str.2019.10.002

Structural Insights into ceNAP1 Chaperoning Activity toward ceH2A-H2B

Structure. 2019 Dec 3;27(12):1798-1810.e3. doi: 10.1016/j.str.2019.10.002. Epub 2019 Oct 22.

Authors

Yongrui Liu¹, Li Xu¹, Changlin Xie¹, Jingjun Hong¹, Fudong Li¹, Ke Ruan¹, Jiajing Chen¹, Jihui Wu², Yunyu Shi³

Affiliations

¹ Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China.
² Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China. Electronic address: wujihui@ustc.edu.cn.
³ Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China. Electronic address: yyshi@ustc.edu.cn.

PMID: 31653339
DOI: 10.1016/j.str.2019.10.002

Abstract

In eukaryotes, nucleosome assembly is crucial for genome integrity. The histone chaperone NAP1 plays an important role in histone folding, storage, and transport, as well as histone exchange and nucleosome assembly. At present, the molecular basis of these activities is not fully understood. We have solved high-resolution crystal structures of Caenorhabditis elegans NAP1 (ceNAP1) in complex with its cognate substrates: the C. elegans H2A-H2B dimer (ceH2A-H2B) and the H2A.Z-H2B dimer (ceH2A.Z-H2B). Our structural and biochemical data reveals the acidic concave surface is relevant to tetramerization, and uncovers how a ceNAP1 homodimer uses its concave surface to asymmetrically recognize a ceH2A-H2B or ceH2A.Z-H2B heterodimer. Intriguingly, an "acidic strip" within the concave surface of ceNAP1 is crucial for binding histones, including H2A-H2B, H3-H4, and histone variants. Thus, our results provide insight into the molecular mechanisms of NAP1 histone chaperone activity.

Keywords: H2A-H2B; H2A.Z-H2B; H3-H4; NAP1; acidic strip; histone chaperone; nucleosome assembly.

Publication types

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

MeSH terms

Amino Acid Sequence
Animals
Binding Sites
Caenorhabditis elegans / genetics*
Caenorhabditis elegans / metabolism
Caenorhabditis elegans Proteins / chemistry*
Caenorhabditis elegans Proteins / genetics
Caenorhabditis elegans Proteins / metabolism
Cloning, Molecular
Crystallography, X-Ray
Escherichia coli / genetics
Escherichia coli / metabolism
Gene Expression
Genetic Vectors / chemistry
Genetic Vectors / metabolism
Histones / chemistry*
Histones / genetics
Histones / metabolism
Models, Molecular
Nucleosome Assembly Protein 1 / chemistry*
Nucleosome Assembly Protein 1 / genetics
Nucleosome Assembly Protein 1 / metabolism
Protein Binding
Protein Conformation, alpha-Helical
Protein Conformation, beta-Strand
Protein Interaction Domains and Motifs
Protein Isoforms / chemistry
Protein Isoforms / genetics
Protein Isoforms / metabolism
Protein Multimerization
Protein Structure, Tertiary
Recombinant Proteins / chemistry
Recombinant Proteins / genetics
Recombinant Proteins / metabolism
Sequence Alignment
Sequence Homology, Amino Acid
Substrate Specificity

Substances

Caenorhabditis elegans Proteins
Histones
Nucleosome Assembly Protein 1
Protein Isoforms
Recombinant Proteins