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, Год журнала: 2024, Номер 3

Опубликована: Дек. 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.

Язык: Английский

Guardians of the Genome: Iron–Sulfur Proteins in the Nucleus DOI Creative Commons
Lorena Novoa‐Aponte, Andrés León-Torres, Caroline C. Philpott

и другие.

Inorganics, Год журнала: 2024, Номер 12(12), С. 316 - 316

Опубликована: Дек. 6, 2024

Iron–sulfur (Fe-S) clusters are essential cofactors found in many proteins the mitochondria, cytosol, and nucleus of cell. These versatile may undergo reversible oxidation–reduction reactions to enable electron transfers; they be structural confer stability a folded protein; regulatory transduce an iron signal that alters function or recipient protein. Of nearly 70 described mammalian cells bind Fe-S clusters, about half localize exclusively partially nucleus, where required for DNA replication repair, telomere maintenance, transcription, mitosis, cell cycle control. Most nuclear cluster interact with DNA, including polymerases, primase, helicases, glycosylases. However, specific roles enzymatic activities these their interplay remain matter debate. Defects metallation cause genome instability alter regulation division proliferation, which hallmarks various genetic diseases cancers. Here, we provide inventory cluster-binding discuss types, binding sites, process acquisition, potential proteins. questions unresolved. We highlight critical gaps our understanding delivery client proteins, mechanistic play enzymes. Taken together, this review brings focus human as hotspot aims inspire new research on metabolism maintenance integrity.

Язык: Английский

Процитировано

0

Bacterial Metallostasis: Metal Sensing, Metalloproteome Remodeling, and Metal Trafficking DOI Creative Commons
Daiana A. Capdevila, Johnma J. Rondón, Katherine A. Edmonds

и другие.

Chemical Reviews, Год журнала: 2024, Номер unknown

Опубликована: Дек. 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

Язык: Английский

Процитировано

0

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

и другие.

Biochemistry, Год журнала: 2024, Номер 64(1), С. 156 - 169

Опубликована: Дек. 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.

Язык: Английский

Процитировано

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, Год журнала: 2024, Номер 3

Опубликована: Дек. 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.

Язык: Английский

Процитировано

0