7v1l
From Proteopedia
Structure of sNASP core in complex with H3 alpha3 helix peptide
Structural highlights
FunctionNASP_HUMAN Required for DNA replication, normal cell cycle progression and cell proliferation. Forms a cytoplasmic complex with HSP90 and H1 linker histones and stimulates HSP90 ATPase activity. NASP and H1 histone are subsequently released from the complex and translocate to the nucleus where the histone is released for binding to DNA.[UniProtKB:Q99MD9] Publication Abstract from PubMedHistone 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 alpha3 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 alpha3 helix and the H3 alphaN region, respectively. Functional studies demonstrate the H3 alphaN-interaction represents the major binding mode of NASP in cells and shielding of the H3 alphaN 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. 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 Nucleic Acids Res. 2022 Apr 30. pii: 6576354. doi: 10.1093/nar/gkac303. PMID:35489058[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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