A Semisynthetic Fusicoccane Stabilizes a Protein-Protein Interaction and Enhances the Expression of K+ Channels at the Cell Surface

被引：95

作者：

Anders, Carolin ^{[1
,4
]}

Higuchi, Yusuke ^{[2
]}

Koschinsky, Kristin ^{[3
]}

Bartel, Maria ^{[1
]}

Schumacher, Benjamin ^{[1
]}

Thiel, Philipp ^{[1
]}

Nitta, Hajime ^{[2
]}

Preisig-Mueller, Regina ^{[3
]}

Schlichthoerl, Guenter ^{[3
]}

Renigunta, Vijay ^{[3
]}

Ohkanda, Junko ^{[2
]}

Daut, Juergen ^{[3
]}

Kato, Nobuo ^{[2
]}

Ottmann, Christian ^{[1
]}

机构：

[1] Max Planck Gesell, Chem Genom Ctr, D-44227 Dortmund, Germany

[2] Osaka Univ, Inst Sci & Ind Res, Osaka 5670047, Japan

[3] Univ Marburg, Inst Physiol & Pathophysiol, D-35037 Marburg, Germany

[4] Eindhoven Univ Technol, NL-5600 MB Eindhoven, Netherlands

来源：

CHEMISTRY & BIOLOGY | 2013年 / 20卷 / 04期

基金：

日本学术振兴会;

关键词：

POTASSIUM CHANNELS; ENDOPLASMIC-RETICULUM; DRUG DISCOVERY; EXOENZYME-S; TASK-3; BINDING; ACTIVATION; TRANSPORT; DOMAIN; KCNK9;

D O I：

10.1016/j.chembiol.2013.03.015

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Small-molecule stabilization of protein-protein interactions is an emerging field in chemical biology. We show how fusicoccanes, originally identified as fungal toxins acting on plants, promote the interaction of 14-3-3 proteins with the human potassium channel TASK-3 and present a semisynthetic fusicoccane derivative (FC-THF) that targets the 14-3-3 recognition motif (mode 3) in TASK-3. In the presence of FC-THF, the binding of 14-3-3 proteins to TASK-3 was increased 19-fold and protein crystallography provided the atomic details of the effects of FC-THF on this interaction. We also tested the functional effects of FC-THF on TASK channels heterologously expressed in Xenopus oocytes. Incubation with 10 mu M FC-THF was found to promote the transport of TASK channels to the cell membrane, leading to a significantly higher density of channels at the surface membrane and increased potassium current.

引用

页码：583 / 593

页数：11

共 45 条

[1]

Maternally inherited Birk barel mental retardation dysmorphism syndrome caused by a mutation in the genomically imprinted potassium channel KCNK9 [J].

Barel, Ortal ;

Shalev, Stavit A. ;

Ofir, Rivka ;

Cohen, Asi ;

Zlotogora, Joel ;

Shorer, Zamir ;

Mazor, Galia ;

Finer, Gal ;

Khateeb, Shareef ;

Zilberberg, Noam ;

Birk, Ohad S. .

AMERICAN JOURNAL OF HUMAN GENETICS, 2008, 83 (02) :193-199

[2]

14-3-3 proteins in the nervous system [J].

Berg, D ;

Holzmann, C ;

Riess, O .

NATURE REVIEWS NEUROSCIENCE, 2003, 4 (09) :752-762

[3]

From the Background to the Spotlight: TASK Channels in Pathological Conditions [J].

Bittner, Stefan ;

Budde, Thomas ;

Wiendl, Heinz ;

Meuth, Sven G. .

BRAIN PATHOLOGY, 2010, 20 (06) :999-1009

[4]

Structure of the FKBP12-rapamycin complex interacting with the binding domain of human FRAP [J].

Choi, JW ;

Chen, J ;

Schreiber, SL ;

Clardy, J .

SCIENCE, 1996, 273 (5272) :239-242

[5]

Deafness associated changes in two-pore domain potassium channels in the rat inferior colliculus [J].

Cui, Y. L. ;

Holt, A. G. ;

Lomax, C. A. ;

Altschuler, R. A. .

NEUROSCIENCE, 2007, 149 (02) :421-433

[6]

Fusicoccanes: diterpenes with surprising biological functions [J].

de Boer, Albertus H. ;

de Vries-van Leeuwen, Ingrid J. .

TRENDS IN PLANT SCIENCE, 2012, 17 (06) :360-368

[7]

TASK, a human background K+ channel to sense external pH variations near physiological pH [J].

Duprat, F ;

Lesage, F ;

Fink, M ;

Reyes, R ;

Heurteaux, C ;

Lazdunski, M .

EMBO JOURNAL, 1997, 16 (17) :5464-5471

[8]

BINDING OF 14-3-3-PROTEINS TO THE PROTEIN-KINASE RAF AND EFFECTS ON ITS ACTIVATION [J].

FREED, E ;

SYMONS, M ;

MACDONALD, SG ;

MCCORMICK, F ;

RUGGIERI, R .

SCIENCE, 1994, 265 (5179) :1713-1716

[9]

THE EUKARYOTIC HOST FACTOR THAT ACTIVATES EXOENZYME-S OF PSEUDOMONAS-AERUGINOSA IS A MEMBER OF THE 14-3-3 PROTEIN FAMILY [J].

FU, H ;

COBURN, J ;

COLLIER, RJ .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (06) :2320-2324

[10]

TASK-3 as a potential antidepressant target [J].

Gotter, Anthony L. ;

Santarelli, Vincent P. ;

Doran, Scott M. ;

Tannenbaum, Pamela L. ;

Kraus, Richard L. ;

Rosahl, Thomas W. ;

Meziane, Hamid ;

Montial, Marina ;

Reiss, Duane R. ;

Wessner, Keith ;

McCampbell, Alexander ;

Stevens, Joanne ;

Brunner, Joseph I. ;

Fox, Steven V. ;

Uebele, Victor N. ;

Bayliss, Douglas A. ;

Winrow, Christopher J. ;

Renger, John J. .

BRAIN RESEARCH, 2011, 1416 :69-79

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