The presence and functions of nuclear actin have been controversial due to the lack of molecular mechanisms.Nuclear actin and actin?『elated proteins (Arps) are subunits of several chromatin remodelers, including the ...The presence and functions of nuclear actin have been controversial due to the lack of molecular mechanisms.Nuclear actin and actin?『elated proteins (Arps) are subunits of several chromatin remodelers, including the evolutionarily conserved IN080 chromatin-remodeling complex. Here, we present an improved cryo-EM structure of the yeast IN080 complex and the first 3D reconstruction of the IN080 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 IN080 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 IN080 ATPase domain. Our findings suggest that the conserved nuclear actin/Arp module acts a conformational switch of the IN080 for nucleosome binding.展开更多
基金the National Natural Science Foundation of China (31570726 and 31170694)the National Basic Research Program (2014CB910700).
文摘The presence and functions of nuclear actin have been controversial due to the lack of molecular mechanisms.Nuclear actin and actin?『elated proteins (Arps) are subunits of several chromatin remodelers, including the evolutionarily conserved IN080 chromatin-remodeling complex. Here, we present an improved cryo-EM structure of the yeast IN080 complex and the first 3D reconstruction of the IN080 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 IN080 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 IN080 ATPase domain. Our findings suggest that the conserved nuclear actin/Arp module acts a conformational switch of the IN080 for nucleosome binding.
