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NASP maintains histone H3–H4 homeostasis through two distinct H3 binding modes
Histone chaperones regulate all aspects of histone metabolism. NASP is a major histone chaperone for H3–H4 dimers critical for preventing histone degradation. Here, we identify two distinct histone binding modes of NASP and reveal how they cooperate to ensure histone H3–H4 supply. We determine the s...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9122598/ https://www.ncbi.nlm.nih.gov/pubmed/35489058 http://dx.doi.org/10.1093/nar/gkac303 |
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author | Bao, Hongyu Carraro, Massimo Flury, Valentin Liu, Yanhong Luo, Min Chen, Liu Groth, Anja Huang, Hongda |
author_facet | Bao, Hongyu Carraro, Massimo Flury, Valentin Liu, Yanhong Luo, Min Chen, Liu Groth, Anja Huang, Hongda |
author_sort | Bao, Hongyu |
collection | PubMed |
description | Histone chaperones regulate all aspects of histone metabolism. NASP is a major histone chaperone for H3–H4 dimers critical for preventing histone degradation. Here, we identify two distinct histone binding modes of NASP and reveal how they cooperate to ensure histone H3–H4 supply. We determine the structures of a sNASP dimer, a complex of a sNASP dimer with two H3 α3 peptides, and the sNASP–H3–H4–ASF1b co-chaperone complex. This captures distinct functionalities of NASP and identifies two distinct binding modes involving the H3 α3 helix and the H3 αN region, respectively. Functional studies demonstrate the H3 αN-interaction represents the major binding mode of NASP in cells and shielding of the H3 αN region by NASP is essential in maintaining the H3–H4 histone soluble pool. In conclusion, our studies uncover the molecular basis of NASP as a major H3–H4 chaperone in guarding histone homeostasis. |
format | Online Article Text |
id | pubmed-9122598 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-91225982022-05-23 NASP maintains histone H3–H4 homeostasis through two distinct H3 binding modes Bao, Hongyu Carraro, Massimo Flury, Valentin Liu, Yanhong Luo, Min Chen, Liu Groth, Anja Huang, Hongda Nucleic Acids Res Structural Biology Histone chaperones regulate all aspects of histone metabolism. NASP is a major histone chaperone for H3–H4 dimers critical for preventing histone degradation. Here, we identify two distinct histone binding modes of NASP and reveal how they cooperate to ensure histone H3–H4 supply. We determine the structures of a sNASP dimer, a complex of a sNASP dimer with two H3 α3 peptides, and the sNASP–H3–H4–ASF1b co-chaperone complex. This captures distinct functionalities of NASP and identifies two distinct binding modes involving the H3 α3 helix and the H3 αN region, respectively. Functional studies demonstrate the H3 αN-interaction represents the major binding mode of NASP in cells and shielding of the H3 αN region by NASP is essential in maintaining the H3–H4 histone soluble pool. In conclusion, our studies uncover the molecular basis of NASP as a major H3–H4 chaperone in guarding histone homeostasis. Oxford University Press 2022-04-30 /pmc/articles/PMC9122598/ /pubmed/35489058 http://dx.doi.org/10.1093/nar/gkac303 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Structural Biology Bao, Hongyu Carraro, Massimo Flury, Valentin Liu, Yanhong Luo, Min Chen, Liu Groth, Anja Huang, Hongda NASP maintains histone H3–H4 homeostasis through two distinct H3 binding modes |
title | NASP maintains histone H3–H4 homeostasis through two distinct H3 binding modes |
title_full | NASP maintains histone H3–H4 homeostasis through two distinct H3 binding modes |
title_fullStr | NASP maintains histone H3–H4 homeostasis through two distinct H3 binding modes |
title_full_unstemmed | NASP maintains histone H3–H4 homeostasis through two distinct H3 binding modes |
title_short | NASP maintains histone H3–H4 homeostasis through two distinct H3 binding modes |
title_sort | nasp maintains histone h3–h4 homeostasis through two distinct h3 binding modes |
topic | Structural Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9122598/ https://www.ncbi.nlm.nih.gov/pubmed/35489058 http://dx.doi.org/10.1093/nar/gkac303 |
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