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Title: Structure of the human histone chaperone FACT Spt16 N-terminal domain

The Spt16–SSRP1 heterodimer is a histone chaperone that plays an important role in regulating chromatin assembly. Here, a crystal structure of the N-terminal domain of human Spt16 is presented and it is shown that this domain may contribute to histone binding. The histone chaperone FACT plays an important role in facilitating nucleosome assembly and disassembly during transcription. FACT is a heterodimeric complex consisting of Spt16 and SSRP1. The N-terminal domain of Spt16 resembles an inactive aminopeptidase. How this domain contributes to the histone chaperone activity of FACT remains elusive. Here, the crystal structure of the N-terminal domain (NTD) of human Spt16 is reported at a resolution of 1.84 Å. The structure adopts an aminopeptidase-like fold similar to those of the Saccharomyces cerevisiae and Schizosaccharomyces pombe Spt16 NTDs. Isothermal titration calorimetry analyses show that human Spt16 NTD binds histones H3/H4 with low-micromolar affinity, suggesting that Spt16 NTD may contribute to histone binding in the FACT complex. Surface-residue conservation and electrostatic analysis reveal a conserved acidic patch that may be involved in histone binding.
Authors:
;  [1]
  1. Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, Scotland (United Kingdom)
Publication Date:
OSTI Identifier:
22515181
Resource Type:
Journal Article
Resource Relation:
Journal Name: Acta Crystallographica. Section F, Structural Biology Communications; Journal Volume: 72; Journal Issue: Pt 2; Other Information: PMCID: PMC4741192; PMID: 26841762; PUBLISHER-ID: hv5313; PUBLISHER-ID: S2053230X15024565; OAI: oai:pubmedcentral.nih.gov:4741192; Copyright (c) Marcianò et al. 2016; This is an open-access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL AND ANALYTICAL CHEMISTRY; 75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND SUPERFLUIDITY; AFFINITY; BREAD; CALORIMETRY; CHROMATIN; COMPLEXES; CRYSTAL STRUCTURE; HISTONES; HUMAN POPULATIONS; HYDROGEN 4; RESIDUES; RESOLUTION; SACCHAROMYCES CEREVISIAE; SURFACES; TITRATION; TRANSCRIPTION