Addition at the Molecular Level: Signal Integration in Designed Per-ARNT-Sim Receptor Proteins

被引:65
作者
Moeglich, Andreas [1 ]
Ayers, Rebecca A. [1 ]
Moffat, Keith [1 ,2 ]
机构
[1] Univ Chicago, Dept Biochem & Mol Biol, Inst Biophys Dynam, Chicago, IL 60637 USA
[2] Univ Chicago, Ctr Adv Radiat Sources, Chicago, IL 60637 USA
基金
美国国家卫生研究院;
关键词
Per-ARNT-Sim; photoreceptor; protein design; signal integration; signal transduction; HISTIDINE KINASE; CRYSTAL-STRUCTURE; LIGAND-BINDING; PAS DOMAINS; LOV DOMAIN; LIGHT; SENSOR; MECHANISM; OXYGEN; TRANSDUCTION;
D O I
10.1016/j.jmb.2010.05.019
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Survival of organisms in dynamic environments requires accurate perception and integration of signals. At the molecular level, signal detection is mediated by signal receptor proteins that largely are of modular composition. Sensor modules, such as the widespread Per-ARNT-Sim (PAS) domains, detect signals and, in response, regulate the biological activity of effector modules. Here, we exploit the modularity of signal receptors to design and engineer synthetic receptors that comprise two PAS sensor domains responsive to different signals, and we use these signals to control the activity of a histidine kinase effector. Designed two-input PAS receptors detected oxygen and blue light in a positive cooperative manner. The extent of the response to the signals was dictated by domain topology: the dominant regulatory effect was exerted by the PAS domain proximal to the effector domain. The presence of one sensor domain modulated the signal response function of the other. Sequence and structural data on natural receptors with tandem PAS domains show that these are predominantly linked by short amphipathic a-helices. Signals from multiple sensor domains could be integrated and propagated to the effector domain as torques. Our results inform the rational design of receptors that integrate multiple signals to modulate cellular behavior. (C) 2010 Elsevier Ltd. All rights reserved.
引用
收藏
页码:477 / 486
页数:10
相关论文
共 45 条
[1]   Regulatory potential, phyletic distribution and evolution of ancient, intracellular small-molecule-binding domains [J].
Anantharaman, V ;
Koonin, EV ;
Aravind, L .
JOURNAL OF MOLECULAR BIOLOGY, 2001, 307 (05) :1271-1292
[2]   The signaling helix: a common functional theme in diverse signaling proteins [J].
Anantharaman, Vivek ;
Balaji, S. ;
Aravind, L. .
BIOLOGY DIRECT, 2006, 1 (1)
[3]  
Aravind L, 2010, SENSORY MECHANISMS IN BACTERIA: MOLECULAR ASPECTS OF SIGNAL RECOGNITION, P1
[4]   Blue light activates the σB-dependent stress response of Bacillus subtilis via YtvA [J].
Avila-Perez, Marcela ;
Hellingwerf, Klaas J. ;
Kort, Remco .
JOURNAL OF BACTERIOLOGY, 2006, 188 (17) :6411-6414
[5]   Changes in Quaternary Structure in the Signaling Mechanisms of PAS Domains [J].
Ayers, Rebecca A. ;
Moffat, Keith .
BIOCHEMISTRY, 2008, 47 (46) :12078-12086
[6]   The Universal Protein Resource (UniProt) [J].
Bairoch, Amos ;
Bougueleret, Lydie ;
Altairac, Severine ;
Amendolia, Valeria ;
Auchincloss, Andrea ;
Puy, Ghislaine Argoud ;
Axelsen, Kristian ;
Baratin, Delphine ;
Blatter, Marie-Claude ;
Boeckmann, Brigitte ;
Bollondi, Laurent ;
Boutet, Emmanuel ;
Quintaje, Silvia Braconi ;
Breuza, Lionel ;
Bridge, Alan ;
Saux, Virginie Bulliard-Le ;
decastro, Edouard ;
Ciampina, Luciane ;
Coral, Danielle ;
Coudert, Elisabeth ;
Cusin, Isabelle ;
David, Fabrice ;
Delbard, Gwennaelle ;
Dornevil, Dolnide ;
Duek-Roggli, Paula ;
Duvaud, Severine ;
Estreicher, Anne ;
Famiglietti, Livia ;
Farriol-Mathis, Nathalie ;
Ferro, Serenella ;
Feuermann, Marc ;
Gasteiger, Elisabeth ;
Gateau, Alain ;
Gehant, Sebastian ;
Gerritsen, Vivienne ;
Gos, Arnaud ;
Gruaz-Gumowski, Nadine ;
Hinz, Ursula ;
Hulo, Chantal ;
Hulo, Nicolas ;
Innocenti, Alessandro ;
James, Janet ;
Jain, Eric ;
Jimenez, Silvia ;
Jungo, Florence ;
Junker, Vivien ;
Keller, Guillaume ;
Lachaize, Corinne ;
Lane-Guermonprez, Lydie ;
Langendijk-Genevaux, Petra .
NUCLEIC ACIDS RESEARCH, 2008, 36 :D190-D195
[7]   Structure and mechanism of a bacterial light-regulated cyclic nucleotide phosphodiesterase [J].
Barends, Thomas R. M. ;
Hartmann, Elisabeth ;
Griese, Julia J. ;
Beitlich, Thorsten ;
Kirienko, Natalia V. ;
Ryjenkov, Dmitri A. ;
Reinstein, Jochen ;
Shoeman, Robert L. ;
Gomelsky, Mark ;
Schlichting, Ilme .
NATURE, 2009, 459 (7249) :1015-U150
[8]   Phototropin blue-light receptors [J].
Christie, John M. .
ANNUAL REVIEW OF PLANT BIOLOGY, 2007, 58 :21-45
[9]   The LOV domain family: Photoresponsive signaling modules coupled to diverse output domains [J].
Crosson, S ;
Rajagopal, S ;
Moffat, K .
BIOCHEMISTRY, 2003, 42 (01) :2-10
[10]   Next-generation optical technologies for illuminating genetically targeted brain circuits [J].
Deisseroth, Karl ;
Feng, Guoping ;
Majewska, Ania K. ;
Miesenbock, Gero ;
Ting, Alice ;
Schnitzer, Mark J. .
JOURNAL OF NEUROSCIENCE, 2006, 26 (41) :10380-10386