scholarly journals Comparative Genomic Analysis of the DUF34 Protein Family Suggests Role as a Metal Ion Chaperone or Insertase

Biomolecules ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1282
Author(s):  
Colbie J. Reed ◽  
Geoffrey Hutinet ◽  
Valérie de Crécy-Lagard
Keyword(s):  
Stress Responses ◽  
Metal Ion ◽  
Ion Homeostasis ◽  
Genomic Analysis ◽  
Protein Family ◽  
Comparative Genomic ◽  
Pathogen Virulence ◽  
Metal Ion Homeostasis ◽  
Domain Of Unknown Function

Members of the DUF34 (domain of unknown function 34) family, also known as the NIF3 protein superfamily, are ubiquitous across superkingdoms. Proteins of this family have been widely annotated as “GTP cyclohydrolase I type 2” through electronic propagation based on one study. Here, the annotation status of this protein family was examined through a comprehensive literature review and integrative bioinformatic analyses that revealed varied pleiotropic associations and phenotypes. This analysis combined with functional complementation studies strongly challenges the current annotation and suggests that DUF34 family members may serve as metal ion insertases, chaperones, or metallocofactor maturases. This general molecular function could explain how DUF34 subgroups participate in highly diversified pathways such as cell differentiation, metal ion homeostasis, pathogen virulence, redox, and universal stress responses.

scholarly journals Comparative Genomic Analysis of the DUF34 Protein Family Suggests Role as a Metal Ion Chaperone or Insertase

2021 ◽  
Author(s):  
Colbie Reed ◽  
Geoffrey Hutinet ◽  
Valérie de Crécy-Lagard
Keyword(s):  
Stress Responses ◽  
Metal Ion ◽  
Ion Homeostasis ◽  
Genomic Analysis ◽  
Protein Family ◽  
Comparative Genomic ◽  
Pathogen Virulence ◽  
Metal Ion Homeostasis ◽  
Domain Of Unknown Function

Members of the DUF34 (domain of unknown function 34) family, also known as the NIF3 protein superfamily, are ubiquitous across superkingdoms. Proteins of this family have been widely annotated as “GTP cyclohydrolase I type 2” through electronic propagation based on one study. Here, the annotation status of this protein family was examined through comprehensive literature review and integrative bioinformatic analyses that revealed varied pleiotropic associations and phenotypes. This analysis combined with functional complementation studies strongly challenges the current annotation and suggests that DUF34 family members may serve as metal ion insertases, chaperones, or metallocofactor maturases. This general molecular function could explain how DUF34 subgroups participate in highly diversified pathways such as cell differentiation, metal ion homeostasis, pathogen virulence, redox and universal stress responses.

scholarly journals Coagulatory Defects in Type-1 and Type-2 Diabetes

2019 ◽  
Vol 20 (24) ◽  
pp. 6345 ◽  
Author(s):  
Amélie I. S. Sobczak ◽  
Alan J. Stewart
Keyword(s):  
Type 2 Diabetes ◽  
Lipid Metabolism ◽  
Cardiovascular Diseases ◽  
Metal Ion ◽  
Ion Homeostasis ◽  
Physiological Changes ◽  
Metal Ion Homeostasis ◽  
Increased Risk

Diabetes (both type-1 and type-2) affects millions of individuals worldwide. A major cause of death for individuals with diabetes is cardiovascular diseases, in part since both types of diabetes lead to physiological changes that affect haemostasis. Those changes include altered concentrations of coagulatory proteins, hyper-activation of platelets, changes in metal ion homeostasis, alterations in lipid metabolism (leading to lipotoxicity in the heart and atherosclerosis), the presence of pro-coagulatory microparticles and endothelial dysfunction. In this review, we explore the different mechanisms by which diabetes leads to an increased risk of developing coagulatory disorders and how this differs between type-1 and type-2 diabetes.

Identification of a SAR8.2 gene in the susceptible host response of Nicotiana benthamiana to Colletotrichum orbiculare

2005 ◽  
Vol 32 (3) ◽  
pp. 259 ◽  
Author(s):  
Xue Chan Shan ◽  
Paul H. Goodwin
Keyword(s):  
Stress Responses ◽  
Nicotiana Benthamiana ◽  
Metal Ion ◽  
Ion Homeostasis ◽  
Virus Induced Gene Silencing ◽  
Colletotrichum Orbiculare ◽  
Cdna Subtraction ◽  
Susceptible Host ◽  
Metal Ion Homeostasis ◽  
C Terminus

A SAR8.2 gene, NbSAR8.2m, was obtained from a PCR-selected cDNA subtraction library constructed from mRNA of Nicotiana benthamiana Domin. infected with Colletotrichum orbiculare (Berk & Mont.) von Arx. It is the first SAR8.2 gene described from N. benthamiana and shows relatively high similarity in both the coding and 3′-UTR to NtSAR8.2m of Nicotiana tabacum L. Expression of NbSAR8.2m occurred in healthy plants but was induced 8-fold following infection by C. orbiculare. Virus-induced gene silencing of NbSAR8.2m reduced its expression and resulted in the development of disease symptoms 24 h earlier than in control plants, indicating that NbSAR8.2m affects the length of the biotrophic phase of infection. Both NtSAR8.2m and NbSAR8.2m are unique among the SAR8.2 genes in that they encode for four cysteines near the C-terminus. The conserved cysteines of SAR8.2 genes may indicate roles in stress responses, defence reactions, metal ion homeostasis or other processes.

scholarly journals Population genomics provides insights in diversity, epidemiology, evolution and pathogenicity of the waterborne pathogen Mycobacterium kansasii

2020 ◽  
Author(s):  
Tao Luo ◽  
Peng Xu ◽  
Yangyi Zhang ◽  
Jessica L. Porter ◽  
Marwan Ghanem ◽  
...  
Keyword(s):  
Metal Ion ◽  
Population Genomics ◽  
Ion Homeostasis ◽  
Metabolic Adaptation ◽  
Nontuberculous Mycobacterium ◽  
Comparative Genomic ◽  
Past Century ◽  
Mycobacterium Kansasii ◽  
Ample Evidence ◽  
Metal Ion Homeostasis

Abstract Mycobacterium kansasii is a nontuberculous mycobacterium that can cause serious pulmonary disease. Genotyping suggested that the species is composed of at least six subtypes that vary in clinical significance, with subtype I being clinically dominant but less commonly isolated from environmental sources. Here we report a population genomics study of 358 M. kansasii isolates obtained from global water and clinical sources. Phylogenomic analyses revealed that the six subtypes are more accurately designated as closely related subspecies. These subspecies show ample evidence of recombination mediated by distributive conjugative transfer that has contributed to subspeciation and on-going diversification. Water was confirmed as a source of clinical infections by showing that genomes of clinical strains from an Australian outbreak were almost indistinguishable from strains contaminating the drinking water supply. Most clinical infections (nearly 80%) were due to a recently emerged group of strains designated the M. kansasii main complex (MKMC), which appears to have originated in Europe in 1900s and expanded globally over the past century. Comparative genomic analyses revealed that the MKMC has maintained the methylcitrate cycle and expanded ESX-I secretion-associated proteins, perhaps facilitating metabolic adaptation and pathogenicity for human hosts. Evidence of on-going positive selection in isolates of the MKMC was found in genes involved in carbon and secondary metabolism, metal ion homeostasis and cell surface remodeling that could represent adaptation to human hosts. These results further our understanding of the epidemiology and pathogenicity of M. kansasii and emphasize the importance of monitoring its potential transition to a more human-adapted pathogen.

scholarly journals Zinc limitation in Klebsiella pneumoniae profiled by quantitative proteomics influences transcriptional regulation and cation transporter-associated capsule production

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
A. Sukumaran ◽  
S. Pladwig ◽  
J. Geddes-McAlister
Keyword(s):  
Klebsiella Pneumoniae ◽  
Metal Ion ◽  
Ion Homeostasis ◽  
Cellular Protein ◽  
Pcr Analysis ◽  
Phenotypic Analysis ◽  
Metal Ion Homeostasis ◽  
Capsule Production ◽  
The Impact

Abstract Background Microbial organisms encounter a variety of environmental conditions, including changes to metal ion availability. Metal ions play an important role in many biological processes for growth and survival. As such, microbes alter their cellular protein levels and secretion patterns in adaptation to a changing environment. This study focuses on Klebsiella pneumoniae, an opportunistic bacterium responsible for nosocomial infections. By using K. pneumoniae, we aim to determine how a nutrient-limited environment (e.g., zinc depletion) modulates the cellular proteome and secretome of the bacterium. By testing virulence in vitro, we provide novel insight into bacterial responses to limited environments in the presence of the host. Results Analysis of intra- and extracellular changes identified 2380 proteins from the total cellular proteome (cell pellet) and 246 secreted proteins (supernatant). Specifically, HutC, a repressor of the histidine utilization operon, showed significantly increased abundance under zinc-replete conditions, which coincided with an expected reduction in expression of genes within the hut operon from our validating qRT-PCR analysis. Additionally, we characterized a putative cation transport regulator, ChaB that showed significantly higher abundance under zinc-replete vs. -limited conditions, suggesting a role in metal ion homeostasis. Phenotypic analysis of a chaB deletion strain demonstrated a reduction in capsule production, zinc-dependent growth and ion utilization, and reduced virulence when compared to the wild-type strain. Conclusions This is first study to comprehensively profile the impact of zinc availability on the proteome and secretome of K. pneumoniae and uncover a novel connection between zinc transport and capsule production in the bacterial system.

scholarly journals Metallothionein: A Multifunctional Protein from Toxicity to Cancer

2003 ◽  
Vol 18 (3) ◽  
pp. 162-169 ◽  
Author(s):  
S.E. Theocharis ◽  
A.P. Margeli ◽  
A. Koutselinis
Keyword(s):  
Cell Proliferation ◽  
Metal Ion ◽  
Defense Mechanisms ◽  
Ion Homeostasis ◽  
Low Molecular Weight ◽  
Multifunctional Protein ◽  
Metal Ion Homeostasis ◽  
Potential Marker ◽  
Proliferation And Apoptosis ◽  
Carcinogenic Process

The metallothionein (MT) family is a class of low molecular weight, intracellular and cysteine-rich proteins presenting high affinity for metal ions. Although the members of this family were discovered nearly 40 years ago, their functional significance remains obscure. Four major MT isoforms, MT-1, MT-2, MT-3 and MT-4, have been identified in mammals. MTs are involved in many pathophysiological processes such as metal ion homeostasis and detoxification, protection against oxidative damage, cell proliferation and apoptosis, chemoresistance and radiotherapy resistance. MT isoforms have been shown to be involved in several aspects of the carcinogenic process, cancer development and progression. MT expression has been implicated as a transient response to any form of stress or injury providing cytoprotective action. Although MT participates in the carcinogenic process, its use as a potential marker of tumor differentiation or cell proliferation, or as a predictor of poor prognosis remains unclear. In the present review the involvement of MT in defense mechanisms to toxicity and in carcinogenicity is discussed.

scholarly journals The novel ECF56 SigG1-RsfG system modulates morphological differentiation and metal-ion homeostasis in Streptomyces tsukubaensis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Rute Oliveira ◽  
Matthew J. Bush ◽  
Sílvia Pires ◽  
Govind Chandra ◽  
Delia Casas-Pastor ◽  
...  
Keyword(s):  
Metal Ion ◽  
Ion Homeostasis ◽  
Morphological Differentiation ◽  
The Novel ◽  
Copper Trafficking ◽  
Streptomyces Tsukubaensis ◽  
Metal Ion Homeostasis ◽  
Σ Factor ◽  
Domain Organisation

AbstractExtracytoplasmic function (ECF) sigma factors are key transcriptional regulators that prokaryotes have evolved to respond to environmental challenges. Streptomyces tsukubaensis harbours 42 ECFs to reprogram stress-responsive gene expression. Among them, SigG1 features a minimal conserved ECF σ2–σ4 architecture and an additional C-terminal extension that encodes a SnoaL_2 domain, which is characteristic for ECF σ factors of group ECF56. Although proteins with such domain organisation are widely found among Actinobacteria, the functional role of ECFs with a fused SnoaL_2 domain remains unknown. Our results show that in addition to predicted self-regulatory intramolecular amino acid interactions between the SnoaL_2 domain and the ECF core, SigG1 activity is controlled by the cognate anti-sigma protein RsfG, encoded by a co-transcribed sigG1-neighbouring gene. Characterisation of ∆sigG1 and ∆rsfG strains combined with RNA-seq and ChIP-seq experiments, suggests the involvement of SigG1 in the morphological differentiation programme of S. tsukubaensis. SigG1 regulates the expression of alanine dehydrogenase, ald and the WhiB-like regulator, wblC required for differentiation, in addition to iron and copper trafficking systems. Overall, our work establishes a model in which the activity of a σ factor of group ECF56, regulates morphogenesis and metal-ions homeostasis during development to ensure the timely progression of multicellular differentiation.

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