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bioRxiv · 10.1101/2021.11.02.467034

NASP maintains histone H3-H4 homeostasis through two distinct H3 binding modes

Bao, H.·Carraro, M.·Flury, V.·Liu, Y.·Luo, M.·Chen, L.·Groth, A.·Huang, H.
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Abstract

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 sNASP with an H3 3 peptide, and the sNASP-H3-H4-ASF1b co-chaperone complex. This captures distinct functionalities of NASP and identifies two distinct binding modes involving the H3 3 helix and the H3 N region, respectively. Functional studies demonstrate the H3 N-interaction represents the major binding mode of NASP in cells and shielding of the H3 N 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.

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Bao, H., Carraro, M., Flury, V., Liu, Y., Luo, M., Chen, L., Groth, A., Huang, H.. 2021-11-03. NASP maintains histone H3-H4 homeostasis through two distinct H3 binding modes. https://doi.org/10.1101/2021.11.02.467034

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