skip to main content
DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

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

Abstract

Here, 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.

Authors:
 [1];  [2];  [1];  [3];  [1];  [1]; ORCiD logo [1];  [1];  [1]
  1. Albert Einstein College of Medicine, Bronx, NY (United States)
  2. Stanford Univ., Menlo Park, CA (United States)
  3. Albert Einstein College of Medicine, Bronx, NY (United States); Rockefeller Univ., New York, NY (United States)
Publication Date:
Research Org.:
SLAC National Accelerator Lab., Menlo Park, CA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1420044
Grant/Contract Number:  
AC02-76SF00515
Resource Type:
Accepted Manuscript
Journal Name:
Nature Communications
Additional Journal Information:
Journal Volume: 8; Journal Issue: 1; Journal ID: ISSN 2041-1723
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY

Citation Formats

Warren, Christopher, Matsui, Tsutomu, Karp, Jerome M., Onikubo, Takashi, Cahill, Sean, Brenowitz, Michael, Cowburn, David, Girvin, Mark, and Shechter, David. Dynamic intramolecular regulation of the histone chaperone nucleoplasmin controls histone binding and release. United States: N. p., 2017. Web. doi:10.1038/s41467-017-02308-3.
Warren, Christopher, Matsui, Tsutomu, Karp, Jerome M., Onikubo, Takashi, Cahill, Sean, Brenowitz, Michael, Cowburn, David, Girvin, Mark, & Shechter, David. Dynamic intramolecular regulation of the histone chaperone nucleoplasmin controls histone binding and release. United States. doi:10.1038/s41467-017-02308-3.
Warren, Christopher, Matsui, Tsutomu, Karp, Jerome M., Onikubo, Takashi, Cahill, Sean, Brenowitz, Michael, Cowburn, David, Girvin, Mark, and Shechter, David. Wed . "Dynamic intramolecular regulation of the histone chaperone nucleoplasmin controls histone binding and release". United States. doi:10.1038/s41467-017-02308-3. https://www.osti.gov/servlets/purl/1420044.
@article{osti_1420044,
title = {Dynamic intramolecular regulation of the histone chaperone nucleoplasmin controls histone binding and release},
author = {Warren, Christopher and Matsui, Tsutomu and Karp, Jerome M. and Onikubo, Takashi and Cahill, Sean and Brenowitz, Michael and Cowburn, David and Girvin, Mark and Shechter, David},
abstractNote = {Here, 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.},
doi = {10.1038/s41467-017-02308-3},
journal = {Nature Communications},
number = 1,
volume = 8,
place = {United States},
year = {2017},
month = {12}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Citation Metrics:
Cited by: 3 works
Citation information provided by
Web of Science

Save / Share:

Works referenced in this record:

The Crystal Structure of Nucleoplasmin-Core
journal, October 2001


Roles of NPM2 in Chromatin and Nucleolar Organization in Oocytes and Embryos
journal, April 2003


Structural insight into how the human helicase subunit MCM2 may act as a histone chaperone together with ASF1 at the replication fork
journal, January 2015

  • Richet, Nicolas; Liu, Danni; Legrand, Pierre
  • Nucleic Acids Research, Vol. 43, Issue 3
  • DOI: 10.1093/nar/gkv021

Histone chaperones in nucleosome eviction and histone exchange
journal, June 2008


Developmentally Regulated Post-translational Modification of Nucleoplasmin Controls Histone Sequestration and Deposition
journal, March 2015


Reconstitution of mitotic chromatids with a minimum set of purified factors
journal, June 2015

  • Shintomi, Keishi; Takahashi, Tatsuro S.; Hirano, Tatsuya
  • Nature Cell Biology, Vol. 17, Issue 8
  • DOI: 10.1038/ncb3187

DAMMIF, a program for rapid ab-initio shape determination in small-angle scattering
journal, January 2009

  • Franke, Daniel; Svergun, Dmitri I.
  • Journal of Applied Crystallography, Vol. 42, Issue 2, p. 342-346
  • DOI: 10.1107/S0021889809000338

Two complexes that contain histones are required for nucleosome assembly in vitro: Role of nucleoplasmin and N1 in Xenopus egg extracts
journal, December 1987


The Amber biomolecular simulation programs
journal, January 2005

  • Case, David A.; Cheatham, Thomas E.; Darden, Tom
  • Journal of Computational Chemistry, Vol. 26, Issue 16
  • DOI: 10.1002/jcc.20290

Determination of the regularization parameter in indirect-transform methods using perceptual criteria
journal, August 1992


Preferential Binding of the Histone (H3-H4) 2 Tetramer by NAP1 Is Mediated by the Amino-terminal Histone Tails
journal, August 2003

  • McBryant, Steven J.; Park, Young-Jun; Abernathy, Stephanie M.
  • Journal of Biological Chemistry, Vol. 278, Issue 45
  • DOI: 10.1074/jbc.M305636200

Nucleosomes are assembled by an acidic protein which binds histones and transfers them to DNA
journal, October 1978

  • Laskey, R. A.; Honda, B. M.; Mills, A. D.
  • Nature, Vol. 275, Issue 5679
  • DOI: 10.1038/275416a0

A Mechanism for Histone Chaperoning Activity of Nucleoplasmin: Thermodynamic and Structural Models
journal, October 2009

  • Taneva, Stefka G.; Bañuelos, Sonia; Falces, Jorge
  • Journal of Molecular Biology, Vol. 393, Issue 2
  • DOI: 10.1016/j.jmb.2009.08.005

Ensemble Approach for NMR Structure Refinement against 1 H Paramagnetic Relaxation Enhancement Data Arising from a Flexible Paramagnetic Group Attached to a Macromolecule
journal, May 2004

  • Iwahara, Junji; Schwieters, Charles D.; Clore, G. Marius
  • Journal of the American Chemical Society, Vol. 126, Issue 18
  • DOI: 10.1021/ja031580d

Chromatin assembly: Cooperation between histone chaperones and ATP-dependent nucleosome remodeling machines
journal, April 2002


Massive phosphorylation distinguishes Xenopus laevis nucleoplasmin isolated from oocytes or unfertilized eggs
journal, September 1986

  • Cotten, Matt; Sealy, Linda; Chalkley, Roger
  • Biochemistry, Vol. 25, Issue 18
  • DOI: 10.1021/bi00366a014

New insights into nucleosome and chromatin structure: an ordered state or a disordered affair?
journal, June 2012

  • Luger, Karolin; Dechassa, Mekonnen L.; Tremethick, David J.
  • Nature Reviews Molecular Cell Biology, Vol. 13, Issue 7
  • DOI: 10.1038/nrm3382

ANP32E is a histone chaperone that removes H2A.Z from chromatin
journal, January 2014

  • Obri, Arnaud; Ouararhni, Khalid; Papin, Christophe
  • Nature, Vol. 505, Issue 7485
  • DOI: 10.1038/nature12922

Fly Fishing for Histones: Catch and Release by Histone Chaperone Intrinsically Disordered Regions and Acidic Stretches
journal, August 2017


Sensitivity of secondary structure propensities to sequence differences between α- and γ-synuclein: Implications for fibrillation
journal, December 2006

  • Marsh, Joseph A.; Singh, Vinay K.; Jia, Zongchao
  • Protein Science, Vol. 15, Issue 12
  • DOI: 10.1110/ps.062465306

Polyglutamylation Is a Post-translational Modification with a Broad Range of Substrates
journal, November 2007

  • van Dijk, Juliette; Miro, Julie; Strub, Jean-Marc
  • Journal of Biological Chemistry, Vol. 283, Issue 7
  • DOI: 10.1074/jbc.M705813200

The Xplor-NIH NMR molecular structure determination package
journal, January 2003


Mutation of the small acidic tract A1 drastically reduces nucleoplasmin activity
journal, September 2004


Two surfaces on the histone chaperone Rtt106 mediate histone binding, replication, and silencing
journal, December 2011

  • Zunder, R. M.; Antczak, A. J.; Berger, J. M.
  • Proceedings of the National Academy of Sciences, Vol. 109, Issue 3
  • DOI: 10.1073/pnas.1119095109

The human histone chaperone sNASP interacts with linker and core histones through distinct mechanisms
journal, September 2011

  • Wang, H.; Ge, Z.; Walsh, S. T. R.
  • Nucleic Acids Research, Vol. 40, Issue 2
  • DOI: 10.1093/nar/gkr781

NMR Characterization of Long-Range Order in Intrinsically Disordered Proteins
journal, June 2010

  • Salmon, Loïc; Nodet, Gabrielle; Ozenne, Valéry
  • Journal of the American Chemical Society, Vol. 132, Issue 24
  • DOI: 10.1021/ja101645g

A Quantitative Characterization of Nucleoplasmin/Histone Complexes Reveals Chaperone Versatility
journal, August 2016

  • Fernández-Rivero, Noelia; Franco, Aitor; Velázquez-Campoy, Adrian
  • Scientific Reports, Vol. 6, Issue 1
  • DOI: 10.1038/srep32114

Crystal structure of the nucleosome core particle at 2.8 Å resolution
journal, September 1997

  • Luger, Karolin; Mäder, Armin W.; Richmond, Robin K.
  • Nature, Vol. 389, Issue 6648
  • DOI: 10.1038/38444

Interaction of Nucleoplasmin with Core Histones
journal, June 2003

  • Arnan, Carme; Saperas, Núria; Prieto, Cèlia
  • Journal of Biological Chemistry, Vol. 278, Issue 33
  • DOI: 10.1074/jbc.M305560200

UCSF Chimera?A visualization system for exploratory research and analysis
journal, January 2004

  • Pettersen, Eric F.; Goddard, Thomas D.; Huang, Conrad C.
  • Journal of Computational Chemistry, Vol. 25, Issue 13
  • DOI: 10.1002/jcc.20084

The histone shuffle: histone chaperones in an energetic dance
journal, September 2010

  • Das, Chandrima; Tyler, Jessica K.; Churchill, Mair E. A.
  • Trends in Biochemical Sciences, Vol. 35, Issue 9
  • DOI: 10.1016/j.tibs.2010.04.001

Probabilistic Interaction Network of Evidence Algorithm and its Application to Complete Labeling of Peak Lists from Protein NMR Spectroscopy
journal, March 2009


Estimation of Protein Secondary Structure from Circular Dichroism Spectra: Comparison of CONTIN, SELCON, and CDSSTR Methods with an Expanded Reference Set
journal, December 2000

  • Sreerama, Narasimha; Woody, Robert W.
  • Analytical Biochemistry, Vol. 287, Issue 2, p. 252-260
  • DOI: 10.1006/abio.2000.4880

Structural Basis of the pH-Dependent Assembly of a Botulinum Neurotoxin Complex
journal, November 2014


Quantitative Characterization of Configurational Space Sampled by HIV-1 Nucleocapsid Using Solution NMR, X-ray Scattering and Protein Engineering
journal, March 2016

  • Deshmukh, Lalit; Schwieters, Charles D.; Grishaev, Alexander
  • ChemPhysChem, Vol. 17, Issue 11
  • DOI: 10.1002/cphc.201600212

Nucleoplasmin Binds Histone H2A-H2B Dimers through Its Distal Face
journal, August 2010

  • Ramos, Isbaal; Martín-Benito, Jaime; Finn, Ron
  • Journal of Biological Chemistry, Vol. 285, Issue 44
  • DOI: 10.1074/jbc.M110.150664

Activation Mechanism of the Nuclear Chaperone Nucleoplasmin: Role of the Core Domain
journal, November 2003

  • Bañuelos, Sonia; Hierro, Aitor; Arizmendi, Jesús M.
  • Journal of Molecular Biology, Vol. 334, Issue 3
  • DOI: 10.1016/j.jmb.2003.09.067

Histone chaperones in nucleosome assembly and human disease
journal, January 2013

  • Burgess, Rebecca J.; Zhang, Zhiguo
  • Nature Structural & Molecular Biology, Vol. 20, Issue 1
  • DOI: 10.1038/nsmb.2461

Particle mesh Ewald: An N ⋅log( N ) method for Ewald sums in large systems
journal, June 1993

  • Darden, Tom; York, Darrin; Pedersen, Lee
  • The Journal of Chemical Physics, Vol. 98, Issue 12
  • DOI: 10.1063/1.464397

The intrinsically disordered distal face of nucleoplasmin recognizes distinct oligomerization states of histones
journal, October 2013

  • Ramos, I.; Fernandez-Rivero, N.; Arranz, R.
  • Nucleic Acids Research, Vol. 42, Issue 2
  • DOI: 10.1093/nar/gkt899

Histone transfer among chaperones
journal, March 2012

  • Liu, Wallace H.; Churchill, Mair E. A.
  • Biochemical Society Transactions, Vol. 40, Issue 2
  • DOI: 10.1042/BST20110737

Intrinsically disordered regions of nucleophosmin/B23 regulate its RNA binding activity through their inter- and intra-molecular association
journal, October 2013

  • Hisaoka, M.; Nagata, K.; Okuwaki, M.
  • Nucleic Acids Research, Vol. 42, Issue 2
  • DOI: 10.1093/nar/gkt897

Protein fold determined by paramagnetic magic-angle spinning solid-state NMR spectroscopy
journal, March 2012

  • Sengupta, Ishita; Nadaud, Philippe S.; Helmus, Jonathan J.
  • Nature Chemistry, Vol. 4, Issue 5
  • DOI: 10.1038/nchem.1299

The Catalytic Subunit of the SWR1 Remodeler Is a Histone Chaperone for the H2A.Z-H2B Dimer
journal, February 2014


New developments in the ATSAS program package for small-angle scattering data analysis
journal, March 2012

  • Petoukhov, Maxim V.; Franke, Daniel; Shkumatov, Alexander V.
  • Journal of Applied Crystallography, Vol. 45, Issue 2
  • DOI: 10.1107/S0021889812007662

Ambiguity assessment of small-angle scattering curves from monodisperse systems
journal, April 2015

  • Petoukhov, Maxim V.; Svergun, Dmitri I.
  • Acta Crystallographica Section D Biological Crystallography, Vol. 71, Issue 5
  • DOI: 10.1107/S1399004715002576

Comparative Protein Structure Modeling Using MODELLER
journal, November 2007

  • Eswar, Narayanan; Webb, Ben; Marti-Renom, Marc A.
  • Current Protocols in Protein Science, Vol. 50, Issue 1
  • DOI: 10.1002/0471140864.ps0209s50

The Histone Chaperone Nap1 Promotes Nucleosome Assembly by Eliminating Nonnucleosomal Histone DNA Interactions
journal, March 2010


Glutamylation of Nap1 modulates histone H1 dynamics and chromosome condensation in Xenopus
journal, April 2015

  • Miller, Kelly E.; Heald, Rebecca
  • The Journal of Cell Biology, Vol. 209, Issue 2
  • DOI: 10.1083/jcb.201412097

Prediction and Functional Analysis of Native Disorder in Proteins from the Three Kingdoms of Life
journal, March 2004


An integrated high-throughput data acquisition system for biological solution X-ray scattering studies
journal, March 2012

  • Martel, Anne; Liu, Ping; Weiss, Thomas M.
  • Journal of Synchrotron Radiation, Vol. 19, Issue 3
  • DOI: 10.1107/S0909049512008072

C-terminal acidic domain of histone chaperone human NAP1 is an efficient binding assistant for histone H2A-H2B, but not H3-H4
journal, February 2016

  • Ohtomo, Hideaki; Akashi, Satoko; Moriwaki, Yoshihito
  • Genes to Cells, Vol. 21, Issue 3
  • DOI: 10.1111/gtc.12339

NMRPipe: A multidimensional spectral processing system based on UNIX pipes
journal, November 1995

  • Delaglio, Frank; Grzesiek, Stephan; Vuister, GeertenW.
  • Journal of Biomolecular NMR, Vol. 6, Issue 3
  • DOI: 10.1007/BF00197809

NMR structure of chaperone Chz1 complexed with histones H2A.Z-H2B
journal, July 2008

  • Zhou, Zheng; Feng, Hanqiao; Hansen, D. Flemming
  • Nature Structural & Molecular Biology, Vol. 15, Issue 8
  • DOI: 10.1038/nsmb.1465

Intrinsically disordered proteins: a 10-year recap
journal, December 2012


FACT Disrupts Nucleosome Structure by Binding H2A-H2B with Conserved Peptide Motifs
journal, October 2015


The CCPN data model for NMR spectroscopy: Development of a software pipeline
journal, April 2005

  • Vranken, Wim F.; Boucher, Wayne; Stevens, Tim J.
  • Proteins: Structure, Function, and Bioinformatics, Vol. 59, Issue 4
  • DOI: 10.1002/prot.20449

Assembly of nucleosomes: the reaction involving X. laevis nucleoplasmin
journal, September 1980


Chaperone Nap1 Shields Histone Surfaces Used in a Nucleosome and Can Put H2A-H2B in an Unconventional Tetrameric Form
journal, September 2013


Phosphorylation of Both Nucleoplasmin Domains Is Required for Activation of Its Chromatin Decondensation Activity
journal, May 2007

  • Bañuelos, Sonia; Omaetxebarria, Miren J.; Ramos, Isbaal
  • Journal of Biological Chemistry, Vol. 282, Issue 29
  • DOI: 10.1074/jbc.M702842200

Electrostatic Interactions at the C-Terminal Domain of Nucleoplasmin Modulate Its Chromatin Decondensation Activity
journal, May 2002

  • Hierro, Aitor; Arizmendi, Jesús M.; Bañuelos, Sonia
  • Biochemistry, Vol. 41, Issue 20
  • DOI: 10.1021/bi020002r

Water Dispersion Interactions Strongly Influence Simulated Structural Properties of Disordered Protein States
journal, April 2015

  • Piana, Stefano; Donchev, Alexander G.; Robustelli, Paul
  • The Journal of Physical Chemistry B, Vol. 119, Issue 16
  • DOI: 10.1021/jp508971m

Architectures of Whole-Module and Bimodular Proteins from the 6-Deoxyerythronolide B Synthase
journal, May 2014

  • Edwards, Andrea L.; Matsui, Tsutomu; Weiss, Thomas M.
  • Journal of Molecular Biology, Vol. 426, Issue 11
  • DOI: 10.1016/j.jmb.2014.03.015

    Works referencing / citing this record:

    Structural insights into the ability of nucleoplasmin to assemble and chaperone histone octamers for DNA deposition
    journal, July 2019


    Structural insights into the ability of nucleoplasmin to assemble and chaperone histone octamers for DNA deposition
    journal, July 2019