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

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:
Grant/Contract Number:
AC02-76SF00515
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
Research Org:
SLAC National Accelerator Lab., Menlo Park, CA (United States)
Sponsoring Org:
USDOE
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
OSTI Identifier:
1420044

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., 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. 2017. "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}
}

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