第1280回生物科学セミナー
Structural characterization of AAA proteins with unexpected machineries revealed by single particle cryo-EM
鈴木 博視（ロックフェラー大学 ポスドク研究員）
2019年06月07日(金) 16:00-17:00 理学部1号館東棟 380号室
AAA (ATPase associated with various activities) proteins have functional diversity and are involved in many fundamental processes in all organisms. Many of them share a ring-shape hexameric arrangement of the conserved AAA modules and can couple nucleotide hydrolysis energy to conformational changes for the remodeling or translocation of various macromolecular substrates. One of the essential AAA protein, Mdn1, involved in ribosome maturation has six non-equivalent AAA domains in a single polypeptide and has been expected to work through a power-stroke motion of the extended C-terminal tail because of the similarity to the microtubule-based motor protein, dynein. However, here we show cryo-EM structures of Mdn1 with a relatively rigid and distant connection between the N-terminal AAA ring and the C-terminal linker domain. The structures in two distinct nucleotide/inhibitor-bound states indicate that the remotely separated domain can be docked onto the AAA ring in a nucleotide state-specific manner by a self-remodeling mechanism. I would also like to show the other case of an AAA protein, in which an unexpected mechanism is suggested, and the technical background of the studies. Characterization of the molecular machineries by X-ray and cryo-EM will provide new insights into the differentiated functional details of a variety of AAA proteins.
