Dynamic intramolecular regulation of the histone chaperone nucleoplasmin controls histone binding and release

Christopher Warren, Tsutomu Matsui, Jerome M. Karp, Takashi Onikubo, Sean M. Cahill, Michael D. Brenowitz, David Cowburn, Mark Girvin, David Shechter

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Nucleoplasmin (Npm) is a highly conserved histone chaperone responsible for the maternal storage and zygotic release of histones H2A/H2B. Npm contains a pentameric N-terminal core domain and an intrinsically disordered C-terminal tail domain. Though intrinsically disordered regions are common among histone chaperones, their roles in histone binding and chaperoning remain unclear. Using an NMR-based approach, here we demonstrate that the Xenopus laevis Npm tail domain controls the binding of histones at its largest acidic stretch (A2) via direct competition with both the C-terminal basic stretch and basic nuclear localization signal. NMR and small-angle X-ray scattering (SAXS) structural analyses allowed us to construct models of both the tail domain and the pentameric complex. Functional analyses demonstrate that these competitive intramolecular interactions negatively regulate Npm histone chaperone activity in vitro. Together these data establish a potentially generalizable mechanism of histone chaperone regulation via dynamic and specific intramolecular shielding of histone interaction sites.

Original languageEnglish (US)
Article number2215
JournalNature Communications
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2017

Fingerprint

Nucleoplasmins
Histone Chaperones
Histones
Tail
Nuclear magnetic resonance
Nuclear Localization Signals
nuclear magnetic resonance
Xenopus laevis
X ray scattering
varespladib methyl
Shielding
shielding
Mothers
X-Rays
interactions
scattering
x rays

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Dynamic intramolecular regulation of the histone chaperone nucleoplasmin controls histone binding and release. / Warren, Christopher; Matsui, Tsutomu; Karp, Jerome M.; Onikubo, Takashi; Cahill, Sean M.; Brenowitz, Michael D.; Cowburn, David; Girvin, Mark; Shechter, David.

In: Nature Communications, Vol. 8, No. 1, 2215, 01.12.2017.

Research output: Contribution to journalArticle

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