Structure and Signaling Mechanism of Per-ARNT-Sim Domains

• Published in: Structure (London) Vol. 17; no. 10; pp. 1282 - 1294
• Main Authors: Möglich, Andreas, Ayers, Rebecca A., Moffat, Keith
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 14.10.2009
• Subjects: Amino Acid Sequence; Animals; Binding Sites; CELLBIO; Coiling; Commonality; Covalence; Dynamics; Effectors; Humans; Models, Molecular; Molecular Sequence Data; PAS; Protein Structure, Tertiary; Protein-Serine-Threonine Kinases - chemistry; Protein-Serine-Threonine Kinases - metabolism; PROTEINS; Sensors; Signal Transduction; SIGNALING; Stimuli; CELLBIO; PROTEINS; SIGNALING
• ISSN: 0969-2126; 1878-4186
• DOI: 10.1016/j.str.2009.08.011

Per-ARNT-Sim (PAS) domains serve as versatile sensor and interaction modules in signal transduction proteins. PAS sensors detect chemical and physical stimuli and regulate the activity of functionally diverse effector domains. In contrast to this chemical, physical, and functional diversity, the structure of the core of PAS domains is broadly conserved and comprises a five-stranded antiparallel β sheet and several α helices. Signals originate within the conserved core and generate structural and dynamic changes predominantly within the β sheet, from which they propagate via amphipathic α-helical and coiled-coil linkers at the N or C termini of the core to the covalently attached effector domain. Effector domains are typically dimeric; their activity appears to be largely regulated by signal-dependent changes in quaternary structure and dynamics. The signaling mechanisms of PAS and other signaling domains share common features, and these commonalities can be exploited to enable structure-based design of artificial photosensors and chemosensors.