The structural basis of human Spt16 N-terminal domain interaction with histone (H3-H4)2 tetramer

Biochem Biophys Res Commun. 2019 Jan 15;508(3):864-870. doi: 10.1016/j.bbrc.2018.11.150. Epub 2018 Dec 7.

Abstract

FACT (Facilitates Chromatin Transactions) is a heterodimeric protein complex involved in RNA polymerase II transcription elongation, playing essential roles in chromatin remodeling during transcription, replication, and DNA damage repair. The FACT subunit hSpt16 is essential for nucleosome reorganization. The N-terminal domain of hSpt16 (hSpt16-NTD) was recently described as a histone (H3-H4)2-binding domain; however, its mode of interaction remains unknown. In this study, we solved the structure of hSpt16-NTD437 at 2.19 Å and found that a long-disordered region (hSpt16-LDR), after the main body of hSpt16-NTD, is a novel histone-binding motif. Furthermore, hSpt16-LDR interaction with (H3-H4)2 is H3 N-terminal tail-independent. Therefore, Spt16-NTD is a histone H3-H4-specific binding domain with a distinct mechanism of interaction between histones and histone chaperones.

Keywords: Aminopeptidase-like domain; FACT; Histone (H3-H4)(2); Histone chaperone; Spt16.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Proteins / chemistry*
  • Cell Cycle Proteins / metabolism
  • Histones / metabolism*
  • Humans
  • Models, Molecular
  • Protein Binding
  • Protein Conformation
  • Protein Interaction Domains and Motifs
  • Transcription Factors / chemistry*
  • Transcription Factors / metabolism
  • Xenopus laevis

Substances

  • Cell Cycle Proteins
  • Histones
  • SUPT16H protein, human
  • Transcription Factors