著者
Toshio YANAGIDA Yoshiharu ISHII
出版者
The Japan Academy
雑誌
Proceedings of the Japan Academy, Series B (ISSN:03862208)
巻号頁・発行日
vol.93, no.2, pp.51-63, 2017-02-10 (Released:2017-02-10)
参考文献数
61
被引用文献数
4 13

Single molecule detection has contributed to our understanding of the unique mechanisms of life. Unlike artificial man-made machines, biological molecular machines integrate thermal noises rather than avoid them. For example, single molecule detection has demonstrated that myosin motors undergo biased Brownian motion for stepwise movement and that single protein molecules spontaneously change their conformation, for switching to interactions with other proteins, in response to thermal fluctuation. Thus, molecular machines have flexibility and efficiency not seen in artificial machines.
著者
Yuki Nakamura Kayo Hibino Toshio Yanagida Yasushi Sako
出版者
一般社団法人 日本生物物理学会
雑誌
Biophysics and Physicobiology (ISSN:21894779)
巻号頁・発行日
vol.13, pp.1-11, 2016 (Released:2016-01-20)
参考文献数
30
被引用文献数
12

Son of sevenless (SOS) is a guanine nucleotide exchange factor that regulates cell behavior by activating the small GTPase RAS. Recent in vitro studies have suggested that an interaction between SOS and the GTP-bound active form of RAS generates a positive feedback loop that propagates RAS activation. However, it remains unclear how the multiple domains of SOS contribute to the regulation of the feedback loop in living cells. Here, we observed single molecules of SOS in living cells to analyze the kinetics and dynamics of SOS behavior. The results indicate that the histone fold and Grb2-binding domains of SOS concertedly produce an intermediate state of SOS on the cell surface. The fraction of the intermediated state was reduced in positive feedback mutants, suggesting that the feedback loop functions during the intermediate state. Translocation of RAF, recognizing the active form of RAS, to the cell surface was almost abolished in the positive feedback mutants. Thus, the concerted functions of multiple membrane-associating domains of SOS governed the positive feedback loop, which is crucial for cell fate decision regulated by RAS.