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Structure of IMPORTIN-4 bound to the H3–H4–ASF1 histone–histone chaperone complex
IMPORTIN-4, the primary nuclear import receptor of core histones H3 and H4, binds the H3–H4 dimer and histone chaperone ASF1 prior to nuclear import. However, how H3–H3–ASF1 is recognized for transport cannot be explained by available crystal structures of IMPORTIN-4–histone tail peptide complexes....
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9499513/ https://www.ncbi.nlm.nih.gov/pubmed/36103578 http://dx.doi.org/10.1073/pnas.2207177119 |
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author | Bernardes, Natália Elisa Fung, Ho Yee Joyce Li, Yang Chen, Zhe Chook, Yuh Min |
author_facet | Bernardes, Natália Elisa Fung, Ho Yee Joyce Li, Yang Chen, Zhe Chook, Yuh Min |
author_sort | Bernardes, Natália Elisa |
collection | PubMed |
description | IMPORTIN-4, the primary nuclear import receptor of core histones H3 and H4, binds the H3–H4 dimer and histone chaperone ASF1 prior to nuclear import. However, how H3–H3–ASF1 is recognized for transport cannot be explained by available crystal structures of IMPORTIN-4–histone tail peptide complexes. Our 3.5-Å IMPORTIN-4–H3–H4–ASF1 cryoelectron microscopy structure reveals the full nuclear import complex and shows a binding mode different from suggested by previous structures. The N-terminal half of IMPORTIN-4 clamps the globular H3–H4 domain and H3 αN helix, while its C-terminal half binds the H3 N-terminal tail weakly; tail contribution to binding energy is negligible. ASF1 binds H3–H4 without contacting IMPORTIN-4. Together, ASF1 and IMPORTIN-4 shield nucleosomal H3–H4 surfaces to chaperone and import it into the nucleus where RanGTP binds IMPORTIN-4, causing large conformational changes to release H3–H4–ASF1. This work explains how full-length H3–H4 binds IMPORTIN-4 in the cytoplasm and how it is released in the nucleus. |
format | Online Article Text |
id | pubmed-9499513 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-94995132023-03-14 Structure of IMPORTIN-4 bound to the H3–H4–ASF1 histone–histone chaperone complex Bernardes, Natália Elisa Fung, Ho Yee Joyce Li, Yang Chen, Zhe Chook, Yuh Min Proc Natl Acad Sci U S A Biological Sciences IMPORTIN-4, the primary nuclear import receptor of core histones H3 and H4, binds the H3–H4 dimer and histone chaperone ASF1 prior to nuclear import. However, how H3–H3–ASF1 is recognized for transport cannot be explained by available crystal structures of IMPORTIN-4–histone tail peptide complexes. Our 3.5-Å IMPORTIN-4–H3–H4–ASF1 cryoelectron microscopy structure reveals the full nuclear import complex and shows a binding mode different from suggested by previous structures. The N-terminal half of IMPORTIN-4 clamps the globular H3–H4 domain and H3 αN helix, while its C-terminal half binds the H3 N-terminal tail weakly; tail contribution to binding energy is negligible. ASF1 binds H3–H4 without contacting IMPORTIN-4. Together, ASF1 and IMPORTIN-4 shield nucleosomal H3–H4 surfaces to chaperone and import it into the nucleus where RanGTP binds IMPORTIN-4, causing large conformational changes to release H3–H4–ASF1. This work explains how full-length H3–H4 binds IMPORTIN-4 in the cytoplasm and how it is released in the nucleus. National Academy of Sciences 2022-09-14 2022-09-20 /pmc/articles/PMC9499513/ /pubmed/36103578 http://dx.doi.org/10.1073/pnas.2207177119 Text en Copyright © 2022 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Biological Sciences Bernardes, Natália Elisa Fung, Ho Yee Joyce Li, Yang Chen, Zhe Chook, Yuh Min Structure of IMPORTIN-4 bound to the H3–H4–ASF1 histone–histone chaperone complex |
title | Structure of IMPORTIN-4 bound to the H3–H4–ASF1 histone–histone chaperone complex |
title_full | Structure of IMPORTIN-4 bound to the H3–H4–ASF1 histone–histone chaperone complex |
title_fullStr | Structure of IMPORTIN-4 bound to the H3–H4–ASF1 histone–histone chaperone complex |
title_full_unstemmed | Structure of IMPORTIN-4 bound to the H3–H4–ASF1 histone–histone chaperone complex |
title_short | Structure of IMPORTIN-4 bound to the H3–H4–ASF1 histone–histone chaperone complex |
title_sort | structure of importin-4 bound to the h3–h4–asf1 histone–histone chaperone complex |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9499513/ https://www.ncbi.nlm.nih.gov/pubmed/36103578 http://dx.doi.org/10.1073/pnas.2207177119 |
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