Understanding CRY2 interactions for optical control of intracellular signaling

被引：84

作者：

Duan, Liting ^{[1
]}

Hope, Jen ^{[1
]}

Ong, Qunxiang ^{[1
]}

Lou, Hsin-Ya ^{[1
]}

Kim, Namdoo ^{[2
,3
,4
]}

McCarthy, Comfrey ^{[5
]}

Acero, Victor ^{[6
]}

Lin, Michael Z. ^{[2
,3
,4
]}

Cui, Bianxiao ^{[1
]}

机构：

[1] Stanford Univ, Dept Chem, Stanford, CA 94305 USA

[2] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA

[3] Stanford Univ, Dept Pediat, Stanford, CA 94305 USA

[4] Stanford Univ, Dept Neurobiol, Stanford, CA 94305 USA

[5] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA

[6] Penn State Univ, Dept Engn Sci, University Pk, PA 16802 USA

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

关键词：

BLUE-LIGHT; OPTOGENETIC CONTROL; MAMMALIAN-CELLS; SPATIOTEMPORAL CONTROL; PROTEIN INTERACTIONS; CRYPTOCHROME; LIVING CELLS; ARABIDOPSIS; DOMAIN; ACTIVATION;

D O I：

10.1038/s41467-017-00648-8

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Arabidopsis cryptochrome 2 (CRY2) can simultaneously undergo light-dependent CRY2-CRY2 homo-oligomerization and CRY2-CIB1 hetero-dimerization, both of which have been widely used to optically control intracellular processes. Applications using CRY2-CIB1 interaction desire minimal CRY2 homo-oligomerization to avoid unintended complications, while those utilizing CRY2-CRY2 interaction prefer robust homo-oligomerization. However, selecting the type of CRY2 interaction has not been possible as the molecular mechanisms underlying CRY2 interactions are unknown. Here we report CRY2-CIB1 and CRY2-CRY2 interactions are governed by well-separated protein interfaces at the two termini of CRY2. N-terminal charges are critical for CRY2-CIB1 interaction. Moreover, two C-terminal charges impact CRY2 homo-oligomerization, with positive charges facilitating oligomerization and negative charges inhibiting it. By engineering C-terminal charges, we develop CRY2high and CRY2low with elevated or suppressed oligomerization respectively, which we use to tune the levels of Raf/MEK/ERK signaling. These results contribute to our understanding of the mechanisms underlying light-induced CRY2 interactions and enhance the controllability of CRY2-based optogenetic systems.

引用

页数：10