Nap1 and Kap114 co-chaperone H2A-H2B and facilitate targeted histone release in the nucleus

Core histones, synthesized and processed in the cytoplasm, must be chaperoned as they are transported into the nucleus for nucleosome assembly. The importin Kap114 transports H2A-H2B into the yeast nucleus, where Ran^GTP facilitates histone release. Kap114 and H2A-H2B also bind the histone chaperone Nap1, but how Nap1 and Kap114 cooperate in transport and nucleosome assembly remains unclear. Here, biochemical and structural analyses show that Kap114, H2A-H2B, and a Nap1 dimer (Nap1₂) associate in the absence and presence of Ran^GTP to form equimolar complexes. A previous study had shown that Ran^GTP reduces Kap114’s ability to chaperone H2A-H2B, but a new cryo-EM structure of the Nap1₂•H2A-H2B•Kap114•Ran^GTP complex explains how both Kap114 and Nap1₂ interact with H2A-H2B, restoring its chaperoning within the assembly while effectively depositing it into nucleosomes. Together, our results suggest that Kap114 and Nap1₂ provide a sheltered path that facilitates the transfer of H2A-H2B from Kap114 to Nap1₂, ultimately directing its specific deposition into nucleosomes.

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