title: Structure of the human histone chaperone FACT Spt16 N-terminal domain.
abstract: 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: Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, Scotland.
authors: G
authors: G
authors: Marcianò
authors: Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, Scotland.
authors: D T
authors: DT
authors: Huang
mesh_terms: D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000378:metabolism*; D003460:Crystallization / Q000379:methods*; D018360:Crystallography, X-Ray / Q000379:methods*; D056488:Histone Chaperones / Q000737:chemistry / Q000378:metabolism; D006657:Histones / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D009707:Nucleosomes; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D056488:Histone Chaperones; D006657:Histones; D009707:Nucleosomes; C489489:SUPT16H protein, human; D014157:Transcription Factors
keywords: FACT; Spt16; aminopeptidase; histone chaperone; histones; pita-bread fold