Structural insights into H2A-H2B and H2A.Z-H2B sliding on histone chaperone NAP1OA
The evolutionarily conserved nucleosome assembly protein 1(NAP1)functions as a histone chaperone for H2AH2B,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(XIH2A-H2B)and with C.elegans H2A.Z-H2B(CeH2A.Z-H2B)at 3.35Åand 2.8Å,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-XIH2A-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 CeNAP1α6-carboxy-terminal(C-terminal)tail by the basic H2A/H2A.ZαN-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 20.7Åalong theα6-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.
Li Xu;Jixing Zhang;Yinsong Wang;Dong Liu;Chuting Zeng;Jiawei Chen;Xiaojing Pan
Institute of Bio-Architecture and Bio-Interactions(IBABI),Shenzhen Medical Academy of Research and Translation(SMART),Shenzhen 518107,ChinaInstitute of Bio-Architecture and Bio-Interactions(IBABI),Shenzhen Medical Academy of Research and Translation(SMART),Shenzhen 518107,ChinaInstitute of Bio-Architecture and Bio-Interactions(IBABI),Shenzhen Medical Academy of Research and Translation(SMART),Shenzhen 518107,ChinaInstitute of Bio-Architecture and Bio-Interactions(IBABI),Shenzhen Medical Academy of Research and Translation(SMART),Shenzhen 518107,ChinaInstitute of Bio-Architecture and Bio-Interactions(IBABI),Shenzhen Medical Academy of Research and Translation(SMART),Shenzhen 518107,ChinaInstitute of Bio-Architecture and Bio-Interactions(IBABI),Shenzhen Medical Academy of Research and Translation(SMART),Shenzhen 518107,ChinaInstitute of Bio-Architecture and Bio-Interactions(IBABI),Shenzhen Medical Academy of Research and Translation(SMART),Shenzhen 518107,China
生物科学
chromatinnucleosome assemblyhistone chaperoneNAP1H2A-H2Bsliding mode
《Acta Biochimica et Biophysica Sinica》 2026 (6)
P.1265-1272,8
supported by the grants from the National Natural Science Foundation of China(No.32401018 to L.X.,Nos.32322039 and 32271252 to X.P.)the National Key R&D Program of China(Nos.2022YFA1206400 to X.P.)from Ministry of Science and Technology of China and the Major Program of Shenzhen Bay Laboratory(No.S241101001)X.P.is supported by the start-up funding from Shenzhen Medical Academy of Research and Translation(SMART).
评论