Year: 2025
Type: article
Abstract: The evolutionarily conserved nucleosome assembly protein 1 (NAP1) functions as a histone chaperone for H2A-H2B, regulating nucleosome assembly and maintaining chromatin integrity. However, the dynamic and variable nature of the interactions between acidic NAP1 and basic H2A-H2B has obscured the molecular basis of its chaperoning activity. Here, we report the crystal structures of Caenorhabditis elegans NAP1 (CeNAP1) in complex with Xenopus laevis H2A-H2B (XlH2A-H2B) and with C. elegans H2A.Z-H2B (CeH2A.Z-H2B) at 3.35 Å and 2.8 Å, respectively. In our structures, H2A/H2A.Z-H2B binds to the acidic concave surface of CeNAP1 in three distinct poses, with two in the CeNAP1-XlH2A-H2B complex and one in the CeNAP1-CeH2A.Z-H2B complex. These poses are different from the two poses observed in the previously reported CeNAP1-CeH2A/H2A.Z-H2B structures. The predominant interaction involves engagement of the acidic CeNAP1 α6-carboxy-terminal (C-terminal) tail by the basic H2A/H2A.Z αN–α1 region, stabilized by salt bridges and electrostatic interactions. A comparative analysis of all five known poses reveals that H2A/H2A.Z-H2B can shift approximately 20.7 Å along the α6-C-terminal tail-C′-terminal tail-α6′ axis. These findings demonstrate a sliding binding mode of H2A/H2A.Z-H2B on NAP1, providing new mechanistic insights into nucleosome assembly activity of histone chaperones.
DOI: 10.3724/abbs.2025241
Authors: Li Xu, Jixing Zhang, Yinsong Wang, Dong Liu, Chuting Zeng, Jiawei Chen, Xiaojing Pan
Institution: Shenzhen Medical Academy of Research and Translation
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: diamond
Awards: G2832321762, G347144111, G7946897792
OpenAlex ID: W4417213712