Structure and functional interactions of INO80 actin/Arp module

• 来源期刊: 分子细胞生物学报（英文版）
• 年，卷（期）: 2019,（5）
• 页码范围: 345-355
• 页数: 11页
• 语种: 英文
• DOI: 10.1093/jmcb/mjy062

摘要

The presence and functions of nuclear actin have been controversial due to the lack of molecular mechanisms.Nuclear actin and actin-related proteins (Arps) are subunits of several chromatin remodelers,including the evolutionarily conserved INO80 chromatin-remodeling complex.Here,we present an improved cryo-EM structure of the yeast INO80 complex and the first 3D reconstruction of the INO80 actin/Arp module.The modular and subunit architecture is defined using a combination of subunit deletion analysis and published crosslinking-mass spectrometry.The functional interactions of the INO80 actin/Arp module with a nucleosome is 3D EM reconstructed in two different binding states.Nucleosomes initially bind to the Arp8 subunit and the substantial conformational changes maximize nucleosome contacts of the actin/Arp module,which could promote the bound nucleosome to be engaged onto the INO80 ATPase domain.Our findings suggest that the conserved nuclear actin/Arp module acts a conformational switch of the INO80 for nucleosome binding.