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Chouchani Lab Scientific Resources
ZnCPT: a resource defining the zinc regulated human proteome - BioRxiv (2024)
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Here we develop ZnCPT, a comprehensive and quantitative mapping of the zinc-regulated cysteine proteome. We define 4807 zinc-regulated protein cysteines, uncovering protein families across major domains of biology that are subject to either constitutive or inducible modification by zinc. ZnCPT enables systematic discovery of zinc-regulated structural, enzymatic, and allosteric functional domains. On this basis, we identify 52 cancer genetic dependencies subject to zinc regulation, and nominate malignancies sensitive to zinc-induced cytotoxicity. We provide ZnCPT as a resource for understanding mechanisms of zinc regulation over protein function.
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OPABAT: a resource for annotation of protein function - Cell (2022)
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OPABAT applies proteomics to outbred tissues, allowing for systematic functional annotation of thousands of orphan proteins. This method leverages proteome co-variation inherent to outbred tissues to systematically identify cooperating proteins. In doing so, OPABAT reconstructs hundreds of established protein networks (validation), and assigns 2,578 orphan proteins to 780 protein networks of known function (novel biology). This resource provides the metabolism community with literally thousands of functional assignments for orphan proteins. OPABAT also identifies several proteins that underlie protection from, or sensitivity to, at least one of 19 different metabolic disease parameters.
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Oximouse: a landscape of protein cysteine redox regulation in tissue physiology - Cell (2020)
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Mammalian tissues engage in specialized physiology that is regulated through reversible modification of protein cysteine residues by reactive oxygen species (ROS). ROS regulate a myriad of biological processes, but the protein targets of ROS modification that drive tissue-specific physiology in vivo are largely unknown. Here, we develop Oximouse, a comprehensive and quantitative mapping of the mouse cysteine redox proteome in vivo. We use Oximouse to establish several paradigms of physiological redox signaling. We define and validate cysteine redox networks within each tissue that are tissue selective and underlie tissue-specific biology. We describe a common mechanism for encoding cysteine redox sensitivity by electrostatic gating. Moreover, we comprehensively identify redox-modified disease networks that remodel in aged mice, establishing a systemic molecular basis for the long-standing proposed links between redox dysregulation and tissue aging. We provide the Oximouse compendium as a framework for understanding mechanisms of redox regulation in physiology and aging.
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