Structural insights into H2A-H2B and H2A.Z-H2B sliding on histone chaperone NAP1

Le résumé fourni par la source

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.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.