The nuclear actin-containing Arp8 module is a linker DNA sensor driving IN080 chromatin remodeling

Knoll, Kilian R.; Eustermann, Sebastian; Niebauer, Vanessa; Oberbeckmann, Elisa; Stoehr, Gabriele; Schall, Kevin; Tosi, Alessandro; Schwarz, Marianne; Buchfellner, Andrea; Korber, Philipp; Hopfner, Karl-Peter (2018): The nuclear actin-containing Arp8 module is a linker DNA sensor driving IN080 chromatin remodeling. In: Nature Structural & Molecular Biology, Vol. 25, No. 9: pp. 823-832

Abstract

Nuclear actin (N-actin) and actin-related proteins (Arps) are critical components of several chromatin modulating complexes, including the chromatin remodeler INO80, but their function is largely elusive. Here, we report the crystal structure of the 180-kDa Arp8 module of Saccharomyces cerevisiae INO80 and establish its role in recognition of extranucleosomal linker DNA. Arp8 engages N-actin in a manner distinct from that of other actin-fold proteins and thereby specifies recruitment of the Arp4-N-actin heterodimer to a segmented scaffold of the helicase-SANT-associated (HSA) domain of Ino80. The helical HSA domain spans over 120 angstrom and provides an extended binding platform for extranucleosomal entry DNA that is required for nucleosome sliding and genome-wide nucleosome positioning. Together with the recent cryo-electron microscopy structure of INO80(Core)-nucleosome complex, our findings suggest an allosteric mechanism by which INO80 senses 40-bp linker DNA to conduct highly processive chromatin remodeling.

• Item Type: Journal article
• Faculties: Medicine
• Research Centers: Center for Integrated Protein Science Munich (CIPSM)
• Subjects: 600 Technology > 610 Medicine and health; 500 Science > 540 Chemistry
• ISSN: 1545-9993
• Language: English