Cysteine-rich zinc finger proteins and the nuclear factor kappa-B pathway DOI Creative Commons

Andrew T. Stoltzfus,

Sarah L. J. Michel

Frontiers in Chemical Biology, Journal Year: 2024, Volume and Issue: 3

Published: Dec. 20, 2024

Inflammation-related disorders, such as autoimmune diseases and cancer, impose a significant global health burden. Zinc finger proteins (ZFs) are ubiquitous metalloproteins which regulate inflammation many biological signaling pathways related to growth, development, immune function. Numerous ZFs involved in the nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) pathway, associating them with inflammation-related that feature chronically elevated pro-inflammatory cytokines. This review highlights predominance NFκB-related summarizes breadth functions these perform. The cysteine-specific post-translational modification (PTM) persulfidation is also discussed context cysteine-rich ZFs, including what known from few available reports on functional implications ZF persulfidation. Persulfidation, mediated by endogenously produced hydrogen sulfide (H 2 S), has recently established role inflammation. work will summarize connections between potential inform development therapies.

Language: Английский

Dual Roles of Reducing Systems in Protein Persulfidation and Depersulfidation DOI Creative Commons
Zhichao Liu, Nicolas Rouhier, Jérémy Couturier

et al.

Antioxidants, Journal Year: 2025, Volume and Issue: 14(1), P. 101 - 101

Published: Jan. 16, 2025

The oxidative modification of specific cysteine residues to persulfides is thought be the main way by which hydrogen sulfide (H2S) exerts its biological and signaling functions. Therefore, protein persulfidation represents an important thiol-switching mechanism as other reversible redox post-translational modifications. Considering their reductase activity but also connections with proteins that generate H2S related molecules, glutaredoxin (GRX) thioredoxin (TRX)-reducing systems have potential dual roles in both depersulfidation. In this review, we will first focus on recent advances describing physiological pathways leading before discussing TRX glutathione/GRX-reducing persulfidation/depersulfidation.

Language: Английский

Citations

1
Zinc and RNA Binding Is Linked to the Conformational Flexibility of ZRANB2: A CCCC-Type Zinc Finger Protein DOI
Matthew S. Hursey,

Abigail D. Reitz,

Kyle C. Kihn

et al.

Biochemistry, Journal Year: 2024, Volume and Issue: 64(1), P. 156 - 169

Published: Dec. 16, 2024

Ran-binding domain-containing protein 2 (ZRANB2) is a zinc finger (ZF) that plays key role in alternative splicing. ZRANB2 composed of two ZF domains contain four invariant cysteine residues per domain. binds RNA targets AGGUAA sequence motifs. Three constructs ZRANB2, ZRANB2-ZF1 (first domain), ZRANB2-ZF2 (second and ZRANB2-2D (both domains), were isolated the apo form shown to bind Zn(II) via UV-visible-monitored competitive titrations with Co(II) as spectroscopic probe. Zn binding each construct led adoption limited secondary structure domain, measured by circular dichroism (CD). Hydrogen-deuterium exchange coupled mass spectrometry (HDX-MS) two-domain construct, ZRANB2-2D, revealed both adopt more rigid upon binding. first domain resulted greater decrease conformational dynamics than second TRA2B pre-mRNA, physiological splicing target, was fluorescence anisotropy (FA), high-affinity found require coordination domains. HDX-MS well optimized sequences single double hexamer additional protection from H/D for presence RNA. Here, observed suggesting larger effect on dynamics. A model zinc-mediated proposed.

Language: Английский

Citations

0
Cysteine-rich zinc finger proteins and the nuclear factor kappa-B pathway DOI Creative Commons

Andrew T. Stoltzfus,

Sarah L. J. Michel

Frontiers in Chemical Biology, Journal Year: 2024, Volume and Issue: 3

Published: Dec. 20, 2024

Inflammation-related disorders, such as autoimmune diseases and cancer, impose a significant global health burden. Zinc finger proteins (ZFs) are ubiquitous metalloproteins which regulate inflammation many biological signaling pathways related to growth, development, immune function. Numerous ZFs involved in the nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) pathway, associating them with inflammation-related that feature chronically elevated pro-inflammatory cytokines. This review highlights predominance NFκB-related summarizes breadth functions these perform. The cysteine-specific post-translational modification (PTM) persulfidation is also discussed context cysteine-rich ZFs, including what known from few available reports on functional implications ZF persulfidation. Persulfidation, mediated by endogenously produced hydrogen sulfide (H 2 S), has recently established role inflammation. work will summarize connections between potential inform development therapies.

Language: Английский

Citations

0