Functional understanding of the versatile protein copper metabolism MURR1 domain 1 (COMMD1) in copper homeostasis

2014 ◽  
Vol 1314 (1) ◽  
pp. 6-14 ◽  
Author(s):  
Alina Fedoseienko ◽  
Paulina Bartuzi ◽  
Bart van de Sluis
Keyword(s):  
Copper Metabolism ◽  
Copper Homeostasis ◽  
Functional Understanding

scholarly journals The Role of Zinc in Copper Homeostasis of Aspergillus fumigatus

2020 ◽  
Vol 21 (20) ◽  
pp. 7665
Author(s):  
Suzie Kang ◽  
Hyewon Seo ◽  
Hee-Soo Moon ◽  
Joon-Ho Kwon ◽  
Yong-Sung Park ◽  
...  
Keyword(s):  
Metal Ion ◽  
Zinc Concentration ◽  
Copper Metabolism ◽  
Copper Homeostasis ◽  
Binding Activity ◽  
Upstream Region ◽  
Growth Defect ◽  
Binding Motif ◽  
Copper Supplementation ◽  
Living Organisms

Copper is an essential metal ion that performs many physiological functions in living organisms. Deletion of Afmac1, which is a copper-responsive transcriptional activator in A. fumigatus, results in a growth defect on aspergillus minimal medium (AMM). Interestingly, we found that zinc starvation suppressed the growth defect of the Δafmac1 strain on AMM. In addition, the growth defect of the Δafmac1 strain was recovered by copper supplementation or introduction of the CtrC gene into the Δafmac1 strain. However, chelation of copper by addition of BCS to AMM failed to recover the growth defect of the Δafmac1 strain. Through Northern blot analysis, we found that zinc starvation upregulated CtrC and CtrA2, which encode membrane copper transporters. Interestingly, we found that the conserved ZafA binding motif 5′-CAA(G)GGT-3′ was present in the upstream region of CtrC and CtrA2 and that mutation of the binding motif led to failure of ZafA binding to the upstream region of CtrC and upregulation of CtrC expression under zinc starvation. Furthermore, the binding activity of ZafA to the upstream region of CtrC was inversely proportional to the zinc concentration, and copper inhibited the binding of ZafA to the upstream region of CtrC under a low zinc concentration. Taken together, these results suggest that ZafA upregulates copper metabolism by binding to the ZafA binding motif in the CtrC promoter region under low zinc concentration, thus regulating copper homeostasis. Furthermore, we found that copper and zinc interact in cells to maintain metal homeostasis.

scholarly journals Copper Acquisition Is Mediated by YcnJ and Regulated by YcnK and CsoR in Bacillus subtilis

2009 ◽  
Vol 191 (7) ◽  
pp. 2362-2370 ◽  
Author(s):  
Shashi Chillappagari ◽  
Marcus Miethke ◽  
Hein Trip ◽  
Oscar P. Kuipers ◽  
Mohamed A. Marahiel
Keyword(s):  
Bacillus Subtilis ◽  
Copper Metabolism ◽  
Copper Homeostasis ◽  
Threshold Level ◽  
Upstream Sequence ◽  
Intracellular Content ◽  
Elevated Expression ◽  
Copper Excess ◽  
Microarray Studies

ABSTRACT Copper is an essential cofactor for many enzymes, and at over a threshold level, it is toxic for all organisms. To understand the mechanisms underlying copper homeostasis of the gram-positive bacterium Bacillus subtilis, we have performed microarray studies under copper-limiting conditions. These studies revealed that the ycnJ gene encodes a protein that plays an important role in copper metabolism, as it shows a significant, eightfold upregulation under copper-limiting conditions and its disruption causes a growth-defective phenotype under copper deprivation as well as a reduced intracellular content of copper. Native gel shift experiments with the periplasmic N-terminal domain of the YcnJ membrane protein (135 residues) disclosed its strong affinity to Cu(II) ions in vitro. Inspection of the upstream sequence of ycnJ revealed that the ycnK gene encodes a putative transcriptional regulator, whose deletion caused an elevated expression of ycnJ, especially under conditions of copper excess. Further studies demonstrated that the recently identified copper efflux regulator CsoR also is involved in the regulation of ycnJ expression, leading to a new model for copper homeostasis in B. subtilis.

scholarly journals Deletion of hepatic Ctr1 reveals its function in copper acquisition and compensatory mechanisms for copper homeostasis

2009 ◽  
Vol 296 (2) ◽  
pp. G356-G364 ◽  
Author(s):  
Heejeong Kim ◽  
Hwa-Young Son ◽  
Sarah M. Bailey ◽  
Jaekwon Lee
Keyword(s):  
Critical Role ◽  
Copper Metabolism ◽  
Copper Homeostasis ◽  
Normal Growth ◽  
Copper Uptake ◽  
Compensatory Mechanisms ◽  
Copper Transporter ◽  
Hepatic Copper ◽  
Urinary Copper ◽  
Copper Transporter 1

Copper is a vital trace element required for normal growth and development of many organisms. To determine the roles for copper transporter 1 (Ctr1) in hepatic copper metabolism and the contribution of the liver to systemic copper homeostasis, we have generated and characterized mice in which Ctr1 is deleted specifically in the liver. These mice express less than 10% residual Ctr1 protein in the liver and exhibit a small but significant growth retardation, which disappears with age. Hepatic copper concentrations and the activities of copper-requiring enzymes are reduced; however, mild copper deficiency relative to Ctr1 protein deficit indicates compensatory mechanisms for copper metabolism. Copper concentrations of other organs did not alter despite the defect in hepatic copper uptake. Whereas biliary copper excretion is reduced, urinary copper concentration in these mice is higher than that of control mice. Our data indicate that Ctr1 plays a critical role in copper acquisition in the liver, and, when Ctr1 expression is compromised, compensatory mechanisms facilitate copper uptake and/or retention in the liver and excretion of copper via urine.

scholarly journals Copper and Anesthesia: Clinical Relevance and Management of Copper Related Disorders

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Adrian Langley ◽  
Charles T. Dameron
Keyword(s):  
Clinical Practice ◽  
Clinical Relevance ◽  
Anesthetic Management ◽  
Copper Metabolism ◽  
Copper Homeostasis ◽  
Daily Clinical Practice ◽  
Narrative Review ◽  
Clinical Implications ◽  
Underlying Pathophysiology

Recent research has implicated abnormal copper homeostasis in the underlying pathophysiology of several clinically important disorders, some of which may be encountered by the anesthetist in daily clinical practice. The purpose of this narrative review is to summarize the physiology and pharmacology of copper, the clinical implications of abnormal copper metabolism, and the subsequent influence of altered copper homeostasis on anesthetic management.

Copper-Induced Epigenetic Changes Shape the Clinical Phenotype in Wilson Disease

2020 ◽  
Vol 27 ◽  
Author(s):  
Daniela Fanni ◽  
Clara Gerosa ◽  
Valeria Marina Nurchi ◽  
Rosita Cappai ◽  
Marta Mureddu ◽  
...  
Keyword(s):  
Wilson Disease ◽  
Clinical Presentation ◽  
Clinical Phenotype ◽  
Methylation Status ◽  
Copper Metabolism ◽  
Epigenetic Factors ◽  
Genetic Changes ◽  
Illness Onset ◽  
Phenotypic Manifestation ◽  
Copper Overload

: Wilson disease is a congenital disorder of copper metabolism whose pathogenesis remains, al least in part, unknown. Subjects carrying the same genotype may show completely different phenotypes, differing for the age at illness onset or for the hepatic, neurologic or psychiatric clinical presentation. The inhability to find a unequivocal correlation between the type of mutation in the ATPase copper transporting beta (ATP7B) gene and the phenotypic manifestation, induced many authors to look for epigenetic factors interacting with the genetic changes. Here the evidences regarding the ability of copper overload to change the global DNA methylation status are discussed.

EU Non-Refoulement: (The Irrelevance of) Territoriality and Pre-Border Controls

2017 ◽  
Author(s):  
Violeta Moreno-Lax
Keyword(s):  
International Human Rights Law ◽  
Eu Law ◽  
Human Rights Law ◽  
Refugee Law ◽  
Functional Understanding ◽  
Scope Of Application ◽  
International Refugee Law ◽  
Border Controls ◽  
The Eu

This chapter identifies the content and scope of application of the EU prohibition of refoulement. Following the ‘cumulative standards’ approach, the analysis incorporates developments in international human rights law (IHRL) and international refugee law (IRL). Taking account of the prominent role of the ECHR and the Refugee Convention (CSR51) as sources of Article 19 CFR, these are the two main instruments taken in consideration. The scope of application of Articles 33 CSR51 and 3 ECHR will be identified in turns. Autonomous requirements of EU law will be determined by reference to the asylum acquis as interpreted by the CJEU. The main focus will be on the establishment of the territorial reach of EU non-refoulement. The idea that it may be territorially confined will be rejected. Drawing on the ‘Fransson paradigm’, a ‘functional’ understanding of the ‘implementation of EU law’ standard under Article 51 CFR will be put forward, as the decisive factor to determine applicability of Charter provisions. The implications of non-refoulement for the different measures of extraterritorial control considered in Part I will be delineated at the end.

Plant carotenoid cleavage oxygenases: structure–function relationships and role in development and metabolism

2019 ◽  
Vol 19 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Manoj Kumar Dhar ◽  
Sonal Mishra ◽  
Archana Bhat ◽  
Sudha Chib ◽  
Sanjana Kaul
Keyword(s):  
Higher Plants ◽  
Domain Architecture ◽  
Heme Iron ◽  
Critical Assessment ◽  
Protein Family ◽  
Regulatory Mechanisms ◽  
Non Heme Iron ◽  
Functional Aspects ◽  
Functional Understanding ◽  
Signal Production

Abstract A plant communicates within itself and with the outside world by deploying an array of agents that include several attractants by virtue of their color and smell. In this category, the contribution of ‘carotenoids and apocarotenoids’ is very significant. Apocarotenoids, the carotenoid-derived compounds, show wide representation among organisms. Their biosynthesis occurs by oxidative cleavage of carotenoids, a high-value reaction, mediated by carotenoid cleavage oxygenases or carotenoid cleavage dioxygenases (CCDs)—a family of non-heme iron enzymes. Structurally, this protein family displays wide diversity but is limited in its distribution among plants. Functionally, this protein family has been recognized to offer a role in phytohormones, volatiles and signal production. Further, their wide presence and clade-specific functional disparity demands a comprehensive account. This review focuses on the critical assessment of CCDs of higher plants, describing recent progress in their functional aspects and regulatory mechanisms, domain architecture, classification and localization. The work also highlights the relevant discussion for further exploration of this multi-prospective protein family for the betterment of its functional understanding and improvement of crops.

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