scholarly journals Copper Sources for Sod1 Activation

Antioxidants ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 500
Author(s):  
Stefanie D. Boyd ◽  
Morgan S. Ullrich ◽  
Amelie Skopp ◽  
Duane D. Winkler
Keyword(s):  
Posttranslational Modification ◽  
Copper Ions ◽  
Copper Chaperone ◽  
Copper Uptake ◽  
Radical Oxygen Species ◽  
Catalytic Center ◽  
Cellular Processes ◽  
Copper Delivery ◽  
Trafficking Molecules ◽  
Copper Incorporation

Copper ions (i.e., copper) are a critical part of several cellular processes, but tight regulation of copper levels and trafficking are required to keep the cell protected from this highly reactive transition metal. Cu, Zn superoxide dismutase (Sod1) protects the cell from the accumulation of radical oxygen species by way of the redox cycling activity of copper in its catalytic center. Multiple posttranslational modification events, including copper incorporation, are reliant on the copper chaperone for Sod1 (Ccs). The high-affinity copper uptake protein (Ctr1) is the main entry point of copper into eukaryotic cells and can directly supply copper to Ccs along with other known intracellular chaperones and trafficking molecules. This review explores the routes of copper delivery that are utilized to activate Sod1 and the usefulness and necessity of each.

scholarly journals Metal-binding mechanism of Cox17, a copper chaperone for cytochrome c oxidase

2004 ◽  
Vol 382 (1) ◽  
pp. 307-314 ◽  
Author(s):  
Peep PALUMAA ◽  
Liina KANGUR ◽  
Anastassia VORONOVA ◽  
Rannar SILLARD
Keyword(s):  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Metal Binding ◽  
Copper Ions ◽  
Copper Chaperone ◽  
Copper Chaperones ◽  
Rate Limiting Step ◽  
Charge State Distributions ◽  
Rate Limiting ◽  
Partner Proteins

Cox17, a copper chaperone for cytochrome c oxidase, is an essential and highly conserved protein. The structure and mechanism of functioning of Cox17 are unknown, and even its metalbinding stoichiometry is elusive. In the present study, we demonstrate, using electrospray ionization–MS, that porcine Cox17 binds co-operatively four Cu+ ions. Cu4Cox17 is stable at pH values above 3 and fluorescence spectra indicate the presence of a solvent-shielded multinuclear Cu(I) cluster. Combining our results with earlier EXAFS results on yeast CuCox17, we suggest that Cu4Cox17 contains a Cu4S6-type cluster. At supramillimolar concentrations, dithiothreitol extracts metals from Cu4Cox17, and an apparent copper dissociation constant KCu=13 fM was calculated from these results. Charge-state distributions of different Cox17 forms suggest that binding of the first Cu+ ion to Cox17 causes a conformational change from an open to a compact state, which may be the rate-limiting step in the formation of Cu4Cox17. Cox17 binds non-co-operatively two Zn2+ ions, but does not bind Ag+ ions, which highlights its extremely high metal-binding specificity. We further demonstrate that porcine Cox17 can also exist in partly oxidized (two disulphide bridges) and fully oxidized (three disulphide bridges) forms. Partly oxidized Cox17 can bind one Cu+ or Zn2+ ion, whereas fully oxidized Cox17 does not bind metals. The metal-binding properties of Cox17 imply that, in contrast with other copper chaperones, Cox17 is designed for the simultaneous transfer of up to four copper ions to partner proteins. Metals can be released from Cox17 by non-oxidative as well as oxidative mechanisms.

Proteasome-Independent Functions of Ubiquitin in Endocytosis and Signaling

Science ◽  
2007 ◽  
Vol 315 (5809) ◽  
pp. 201-205 ◽  
Author(s):  
Debdyuti Mukhopadhyay ◽  
Howard Riezman
Keyword(s):  
Neurodegenerative Disorders ◽  
Posttranslational Modification ◽  
Protein Trafficking ◽  
Cellular Proteins ◽  
Cellular Processes ◽  
Signal Transduction Protein ◽  
Major Player ◽  
Independent Functions ◽  
Inflammatory Immune Response ◽  
Ubiquitination System

Ubiquitination is a reversible posttranslational modification of cellular proteins, in which a 76–amino acid polypeptide, ubiquitin, is primarily attached to the ϵ-amino group of lysines in target proteins. Ubiquitination is a major player in regulating a broad host of cellular processes, including cell division, differentiation, signal transduction, protein trafficking, and quality control. Aberrations in the ubiquitination system are implicated in pathogenesis of some diseases, certain malignancies, neurodegenerative disorders, and pathologies of the inflammatory immune response. Here, we discuss the proteasome-independent roles of ubiquitination in signaling and endocytosis.

scholarly journals EF-P Is Essential for Rapid Synthesis of Proteins Containing Consecutive Proline Residues

Science ◽  
2012 ◽  
Vol 339 (6115) ◽  
pp. 85-88 ◽  
Author(s):  
Lili K. Doerfel ◽  
Ingo Wohlgemuth ◽  
Christina Kothe ◽  
Frank Peske ◽  
Henning Urlaub ◽  
...  
Keyword(s):  
Unknown Function ◽  
Bond Formation ◽  
Elongation Factor ◽  
Peptide Bond ◽  
Transfer Rna ◽  
Peptide Bond Formation ◽  
Rapid Synthesis ◽  
Catalytic Center ◽  
Cellular Processes ◽  
Peptidyl Transfer

Elongation factor P (EF-P) is a translation factor of unknown function that has been implicated in a great variety of cellular processes. Here, we show that EF-P prevents ribosome from stalling during synthesis of proteins containing consecutive prolines, such as PPG, PPP, or longer proline strings, in natural and engineered model proteins. EF-P promotes peptide-bond formation and stabilizes the peptidyl–transfer RNA in the catalytic center of the ribosome. EF-P is posttranslationally modified by a hydroxylated β-lysine attached to a lysine residue. The modification enhances the catalytic proficiency of the factor mainly by increasing its affinity to the ribosome. We propose that EF-P and its eukaryotic homolog, eIF5A, are essential for the synthesis of a subset of proteins containing proline stretches in all cells.

scholarly journals Allosteric activation of SENP1 by SUMO1 β-grasp domain involves a dock-and-coalesce mechanism

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Jingjing Guo ◽  
Huan-Xiang Zhou
Keyword(s):  
Cysteine Proteases ◽  
Distal Portion ◽  
Distal Region ◽  
Dynamic Changes ◽  
Catalytic Center ◽  
Cellular Processes ◽  
Correlated Motions ◽  
C Terminus ◽  
Nanosecond Dynamics ◽  
Dynamics Simulations

Small ubiquitin-related modifiers (SUMOs) are conjugated to proteins to regulate a variety of cellular processes. SENPs are cysteine proteases with a catalytic center located within a channel between two subdomains that catalyzes SUMO C-terminal cleavage for processing of SUMO precursors and de-SUMOylation of target proteins. The β-grasp domain of SUMOs binds to an exosite cleft, and allosterically activates SENPs via an unknown mechanism. Our molecular dynamics simulations showed that binding of the β-grasp domain induces significant conformational and dynamic changes in SENP1, including widening of the exosite cleft and quenching of nanosecond dynamics in all but a distal region. A dock-and-coalesce mechanism emerges for SENP-catalyzed SUMO cleavage: the wedging of the β-grasp domain enables the docking of the proximal portion of the C-terminus and the strengthened cross-channel motional coupling initiates inter-subdomain correlated motions to allow for the distal portion to coalesce around the catalytic center.

scholarly journals Copper chaperone blocks amyloid formation via ternary complex

2018 ◽  
Vol 51 ◽  
Author(s):  
Istvan Horvath ◽  
Tony Werner ◽  
Ranjeet Kumar ◽  
Pernilla Wittung-Stafshede
Keyword(s):  
Control Systems ◽  
Protein Misfolding ◽  
Ternary Complex ◽  
Copper Ions ◽  
Copper Chaperone ◽  
Amyloid Formation ◽  
Cellular Environment ◽  
Copper Site ◽  
Amyloidogenic Protein

AbstractProtein misfolding in cells is avoided by a network of protein chaperones that detect misfolded or partially folded species. When proteins escape these control systems, misfolding may result in protein aggregation and amyloid formation. We here show that aggregation of the amyloidogenic protein α-synuclein (αS), the key player in Parkinson's disease, is controlled by the copper transport protein Atox1 in vitro. Copper ions are not freely available in the cellular environment, but when provided by Atox1, the resulting copper-dependent ternary complex blocks αS aggregation. Because the same inhibition was found for a truncated version of αS, lacking the C-terminal part, it appears that Atox1 interacts with the N-terminal copper site in αS. Metal-dependent chaperoning may be yet another manner in which cells control its proteome.

scholarly journals Bacterial Killing by Dry Metallic Copper Surfaces

2010 ◽  
Vol 77 (3) ◽  
pp. 794-802 ◽  
Author(s):  
Christophe Espírito Santo ◽  
Ee Wen Lam ◽  
Christian G. Elowsky ◽  
Davide Quaranta ◽  
Dylan W. Domaille ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Scientific Explanation ◽  
Copper Ions ◽  
Metallic Copper ◽  
Membrane Damage ◽  
Dna Lesions ◽  
Cell Integrity ◽  
Copper Uptake ◽  
Bacterial Killing ◽  
Copper Surfaces

ABSTRACTMetallic copper surfaces rapidly and efficiently kill bacteria. Cells exposed to copper surfaces accumulated large amounts of copper ions, and this copper uptake was faster from dry copper than from moist copper. Cells suffered extensive membrane damage within minutes of exposure to dry copper. Further, cells removed from copper showed loss of cell integrity. Acute contact with metallic copper surfaces did not result in increased mutation rates or DNA lesions. These findings are important first steps for revealing the molecular sensitive targets in cells lethally challenged by exposure to copper surfaces and provide a scientific explanation for the use of copper surfaces as antimicrobial agents for supporting public hygiene.

scholarly journals Functional and Expression Analyses of the cop Operon, Required for Copper Resistance in Agrobacterium tumefaciens

2009 ◽  
Vol 191 (16) ◽  
pp. 5159-5168 ◽  
Author(s):  
Sirikan Nawapan ◽  
Nisanart Charoenlap ◽  
Anchalee Charoenwuttitam ◽  
Panatda Saenkham ◽  
Skorn Mongkolsuk ◽  
...  
Keyword(s):  
Agrobacterium Tumefaciens ◽  
Copper Ions ◽  
Protein A ◽  
Copper Resistance ◽  
Copper Chaperone ◽  
Phytopathogenic Bacterium ◽  
Ion Concentrations ◽  
Increased Sensitivity ◽  
Cop Operon

ABSTRACT The copper resistance determinant copARZ, which encodes a CPx-type copper ATPase efflux protein, a transcriptional regulator, and a putative intracellular copper chaperone, was functionally characterized for the phytopathogenic bacterium Agrobacterium tumefaciens. These genes are transcribed as an operon, and their expression is induced in response to increasing copper and silver ion concentrations in a copR-dependent fashion. Analysis of the copARZ promoter revealed a putative CopR binding box located within the spacer of the −35 and −10 promoter motifs. In vitro, purified CopR could specifically bind to the box. The inactivation of the copARZ operon or copZ reduces the level of resistance to copper but not to other metal ions. Also, the copARZ operon mutant shows increased sensitivity to the superoxide generators menadione and plumbagin. In addition, the loss of functional copZ does not affect the ability of copper ions to induce the copARZ promoter, indicating that CopZ is not involved in the copper-sensing mechanism of CopR. Altogether, the results demonstrate a crucial role for the copARZ operon as a component of the copper resistance machinery in A. tumefaciens.

scholarly journals Recombinant human hyaluronan synthase 3 is phosphorylated in mammalian cells

2006 ◽  
Vol 396 (2) ◽  
pp. 347-354 ◽  
Author(s):  
Brian J. Goentzel ◽  
Paul H. Weigel ◽  
Robert A. Steinberg
Keyword(s):  
Posttranslational Modification ◽  
Mammalian Cells ◽  
Enhanced Green Fluorescent Protein ◽  
Fluorescent Protein ◽  
Hyaluronan Synthase ◽  
Cellular Processes ◽  
Hyaluronan Synthases ◽  
Reference Protein ◽  
Green Fluorescent ◽  
Made In

Hyaluronan is a ubiquitous component of vertebrate extracellular and cell-associated matrices that serves as a key structural component of skin, cartilage, eyes and joints, and plays important roles in dynamic cellular processes, including embryogenesis, inflammation, wound healing and metastasis. Hyaluronan is synthesized by three homologous hyaluronan synthases designated HAS1, HAS2 and HAS3 that differ in their tissue distribution, regulation and enzymatic characteristics. Some progress has been made in characterizing regulation of HAS transcripts and in distinguishing the enzymatic properties of the various HAS isoforms, but essentially nothing is known about their possible regulation by posttranslational modification. Using [32P]Pi radiolabelling of a recombinant FLAG (DYKDDDDK) epitope-tagged version of human HAS3 expressed in COS-7 cells, we show that HAS3 is serine-phosphorylated and that this phosphorylation can be enhanced by a number of effectors – most significantly by a membrane-permeable analogue of cAMP. By employing a novel FLAG-tagged phosphorylated reference protein derived from EGFP (enhanced green fluorescent protein), we were able to estimate the stoichiometry of FLAG–HAS3 phosphorylation. It was approx. 0.11 in unstimulated cells and increased to as much as 0.32 in cells stimulated with 8-(4-chlorophenylthio)-cAMP.

Computational identification of protein S-sulfenylation sites by incorporating the multiple sequence features information

2017 ◽  
Vol 13 (12) ◽  
pp. 2545-2550 ◽  
Author(s):  
Md. Mehedi Hasan ◽  
Dianjing Guo ◽  
Hiroyuki Kurata
Keyword(s):  
Protein Structure ◽  
Posttranslational Modification ◽  
Protein S ◽  
Structure And Function ◽  
Major Type ◽  
Multiple Sequence ◽  
Sequence Features ◽  
Cellular Processes ◽  
Computational Identification ◽  
And Function

Cysteine S-sulfenylation is a major type of posttranslational modification that contributes to protein structure and function regulation in many cellular processes.

scholarly journals Mechanistic insights into the three steps of poly(ADP-ribosylation) reversal

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Johannes Gregor Matthias Rack ◽  
Qiang Liu ◽  
Valentina Zorzini ◽  
Jim Voorneveld ◽  
Antonio Ariza ◽  
...  
Keyword(s):  
Dna Damage ◽  
Structural Analysis ◽  
Dna Damage Response ◽  
Posttranslational Modification ◽  
Molecular Basis ◽  
Branched Polymers ◽  
Coordination Geometry ◽  
Cellular Processes ◽  
Damage Response ◽  
Hydrolysis Of

AbstractPoly(ADP-ribosyl)ation (PAR) is a versatile and complex posttranslational modification composed of repeating units of ADP-ribose arranged into linear or branched polymers. This scaffold is linked to the regulation of many of cellular processes including the DNA damage response, alteration of chromatin structure and Wnt signalling. Despite decades of research, the principles and mechanisms underlying all steps of PAR removal remain actively studied. In this work, we synthesise well-defined PAR branch point molecules and demonstrate that PARG, but not ARH3, can resolve this distinct PAR architecture. Structural analysis of ARH3 in complex with dimeric ADP-ribose as well as an ADP-ribosylated peptide reveal the molecular basis for the hydrolysis of linear and terminal ADP-ribose linkages. We find that ARH3-dependent hydrolysis requires both rearrangement of a catalytic glutamate and induction of an unusual, square-pyramidal magnesium coordination geometry.

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