Vazquez-Rivera Emmanuel, Rojas Brenda, Parrott Jessica C, Shen Anna L, Xing Yongna, Carney Patrick R, Bradfield Christopher A
Molecular and Environmental Toxicology Center, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, United States.
McArdle Laboratory for Cancer Research, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, United States.
Toxicol Rep. 2021 Nov 26;9:1-11. doi: 10.1016/j.toxrep.2021.11.017. eCollection 2022.
Proteins containing PER-ARNT-SIM (PAS) domains are commonly associated with environmental adaptation in a variety of organisms. The PAS domain is found in proteins throughout Archaea, Bacteria, and Eukarya and often binds small-molecules, supports protein-protein interactions, and transduces input signals to mediate an adaptive physiological response. Signaling events mediated by PAS sensors can occur through induced phosphorelays or genomic events that are often dependent upon PAS domain interactions. In this perspective, we briefly discuss the diversity of PAS domain containing proteins, with particular emphasis on the prototype member, the aryl hydrocarbon receptor (AHR). This ligand-activated transcription factor acts as a sensor of the chemical environment in humans and many chordates. We conclude with the idea that since mammalian PAS proteins often act through PAS-PAS dimers, undocumented interactions of this type may link biological processes that we currently think of as independent. To support this idea, we present a framework to guide future experiments aimed at fully elucidating the spectrum of PAS-PAS interactions with an eye towards understanding how they might influence environmental sensing in human and wildlife populations.
含有PER-ARNT-SIM（PAS）结构域的蛋白质通常与多种生物体的环境适应性相关。PAS结构域存在于古细菌、细菌和真核生物的蛋白质中，常与小分子结合，支持蛋白质-蛋白质相互作用，并转导输入信号以介导适应性生理反应。由PAS传感器介导的信号事件可通过诱导的磷酸化信号转导或通常依赖于PAS结构域相互作用的基因组事件发生。从这个角度出发，我们简要讨论了含PAS结构域蛋白质的多样性，特别强调了原型成员芳烃受体（AHR）。这种配体激活的转录因子是人类和许多脊索动物化学环境的传感器。我们的结论是，由于哺乳动物的PAS蛋白通常通过PAS-PAS二聚体起作用，这种未被记录的相互作用可能会将我们目前认为相互独立的生物过程联系起来。为支持这一观点，我们提出了一个框架，以指导未来的实验，旨在全面阐明PAS-PAS相互作用的范围，以期了解它们如何影响人类和野生动物群体的环境感知。
