Bacterial Metallostasis: Metal Sensing, Metalloproteome Remodeling, and Metal Trafficking

Chemical Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 10, 2024

Transition metals function as structural and catalytic cofactors for a large diversity of proteins enzymes that collectively comprise the metalloproteome. Metallostasis considers all cellular processes, notably metal sensing, metalloproteome remodeling, trafficking (or allocation) ensure functional integrity adaptability Bacteria employ both protein RNA-based mechanisms sense intracellular transition bioavailability orchestrate systems-level outputs maintain metallostasis. In this review, we contextualize metallostasis by briefly discussing specialized roles play in biology. We then offer comprehensive perspective on metalloregulatory metal-sensing riboswitches, defining general principles within each sensor superfamily capture how specificity is encoded sequence, selectivity can be leveraged downstream synthetic biology biotechnology applications. This followed discussion recent work highlights selected outputs, including remodeling allocation metallochaperones to client compartments. close places where more needed fill gaps our understanding

Language: Английский

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Triaging of ⍺-helical proteins to the mitochondrial outer membrane by distinct chaperone machinery based on substrate topology

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 17, 2023

SUMMARY Mitochondrial outer membrane ⍺-helical proteins play critical roles in mitochondrial-cytoplasmic communication, but the rules governing targeting and insertion of these biophysically diverse substrates remain unknown. Here, we first defined complement required mammalian biogenesis machinery through genome-wide CRISPRi screens using topologically distinct proteins. Systematic analysis nine identified factors across 21 reveals that components are organized into pathways which act on based their topology. NAC is for efficient polytopic whereas signal-anchored require TTC1, a novel cytosolic chaperone physically engages substrates. Biochemical mutational studies reveal TTC1 employs conserved TPR domain hydrophobic groove its C-terminal to support substrate solubilization mitochondria. Thus, mitochondrial achieved topological triaging cytosol principles with similarities ER protein systems.

Language: Английский

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Protein quality control: from molecular mechanisms to therapeutic intervention—EMBO workshop, May 21–26 2023, Srebreno, Croatia

Cell Stress and Chaperones, Journal Year: 2023, Volume and Issue: 28(6), P. 631 - 640

Published: Sept. 20, 2023

Protein quality control pathways ensure a functional proteome and rely on complex proteostasis network (PN) that is composed of molecular chaperones proteases. Failures in the PN can lead to broad spectrum diseases, including neurodegenerative disorders like Alzheimer's, Parkinson's, range motor neuron diseases. The EMBO workshop "Protein control: from mechanisms therapeutic intervention" covered all aspects protein underlying proteases stress signaling medical implications. This report summarizes highlights selected presentations.

Language: Английский

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