Structure, Folding and Stability of Nucleoside Diphosphate Kinases

Georgescauld, Florian; Song, Yuyu; Dautant, Alain

doi:10.3390/ijms21186779

Cited by 19 publications

(5 citation statements)

References 88 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The resulting monomeric form of HMG-CoA reductase would then become a prime substrate for rapid proteolysis (Cheng et al, 1999). In another example, nucleoside diphosphate kinases (NDPK) are functional as tetramers or hexamers, with these higher-order oligomers displaying greater thermostability through the additional interactions between the dimeric and monomeric forms of NDPKs (Georgescauld et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

SalmonellaYqiC exerts its function through an oligomeric state

Huang

Chen

et al. 2023

Protein Science

View full text Add to dashboard Cite

Protein oligomerization occurs frequently both in vitro and in vivo, with specific functionalities associated with different oligomeric states. The YqiC protein from Salmonella Typhimurium forms a homotrimer through its C‐terminal coiled‐coil domain, and the protein is closely linked to the colonization and invasion of the bacteria to the host cells. To elucidate the importance of the oligomeric state of YqiC in vivo and its relation with bacterial infection, we mutated crucial residues in YqiC's coiled‐coil region and confirmed the loss of trimer formation using chemical crosslinking and Size Exclusion Chromatography coupled with Multiple Angle Light Scattering (SEC‐MALS) techniques. The yqiC‐knockout strain complemented with mutant YqiC showed significantly reduced colonization and invasion of Salmonella to host cells, demonstrating the critical role of YqiC oligomerization in bacterial pathogenesis. Furthermore, we conducted a protein‐protein interaction study of YqiC using a pulled‐down assay coupled with mass spectrometry analysis to investigate the protein's role in bacterial virulence. The results reveal that YqiC interacts with subunits of Complex II of the electron transport chain (SdhA and SdhB) and the β‐subunit of F0F1‐ATP synthase. These interactions suggest that YqiC may modulate the energy production of Salmonella and subsequently affect the assembly of crucial virulence factors, such as flagella. Overall, our findings provide new insights into the molecular mechanisms of YqiC's role in S. Typhimurium pathogenesis and suggest potential therapeutic targets for bacterial infections.This article is protected by copyright. All rights reserved.

show abstract

Section: Discussionmentioning

confidence: 99%

SalmonellaYqiC exerts its function through an oligomeric state

Huang

Chen

et al. 2023

Protein Science

View full text Add to dashboard Cite

show abstract

“…It is suggested that NME1 forms a homogenous trimeric or hexameric complex. 8 It is involved in cell proliferation, differentiation and development, signal transduction, G protein-coupled receptor endocytosis, and gene expression. To date, no reported human phenotype is associated with deleterious variants of the NME1 .…”

Section: Introductionmentioning

confidence: 99%

Revisiting Exome Data Identified Missed Splice Site Variant of the Asparagine Synthetase (ASNS) Gene

et al. 2022

View full text Add to dashboard Cite

Next-generation sequencing, such as whole-exome sequencing (WES), is increasingly used in the study of Mendelian disorders, yet many are reported as “negative.” Inappropriate variant annotation and filtering steps are reasons for missing the molecular diagnosis. Noncoding variants, including splicing mutations, are examples of variants that can be overlooked. Herein, we report a family of four affected newborns, and all presented with severe congenital microcephaly. Initial research WES analysis identified a damaging homozygous variant in NME1 gene as a possible cause of primary microcephaly phenotype in these patients. However, reanalysis of the exome data uncovered a biallelic splice site variant in asparagine synthetase gene which seems to be the possible cause of the phenotype in these patients. This study highlights the importance of revisiting the exome data and the issue of “negative” exome and the afterward approaches to identify and prove new candidate genes.

show abstract

“…Several crystal structures of canonical NDPKs from different organisms have been solved, including bacteria, fungi, amoebas, plants, mammals, protist and even viruses. 10 These determinations revealed different structural assemblies for the NDPKs, which can be found as dimers, tetramers or hexamers. Tetramers are commonly found in prokaryotes while hexamers in eukaryotes.…”

mentioning

confidence: 98%

“… 9 This family includes evolutionarily conserved proteins present in prokaryotes, eukaryotes and also in some viruses. 10 In vertebrates, the NME/NDPK family is composed of ten proteins (NME1 to 10) which are divided in two groups based on phylogenetic analyses. 11 , 12 , 13 Group I corresponds to canonical NDPKs NME1 to 4, sharing 58 to 88% identity with each other and all isoforms present NDPK catalytic activity; group II (NME5 to 10) is comprised of more divergent proteins, which share only 25 to 45% identity with group I and between each other.…”

mentioning

confidence: 99%

Revisiting trypanosomatid nucleoside diphosphate kinases

Miranda

Sayé

Reigada

et al. 2021

Mem. Inst. Oswaldo Cruz

View full text Add to dashboard Cite

BACKGROUND An increasing amount of research has led to the positioning of nucleoside diphosphate kinases (NDPK/NDK) as key metabolic enzymes among all organisms. They contribute to the maintenance the intracellular di-and tri-phosphate nucleoside homeostasis, but they also are involved in widely diverse processes such as gene regulation, apoptosis, signal transduction and many other regulatory roles.OBJETIVE Examine in depth the NDPKs of trypanosomatid parasites responsible for devastating human diseases (e.g., Trypanosoma cruzi, Trypanosoma brucei and Leishmania spp.) which deserve special attention.METHODS The earliest and latest advances in the topic were explored, focusing on trypanosomatid NDPK features, multifunctionality and suitability as molecular drug targets.FINDINGS Trypanosomatid NDPKs appear to play functions different from their host counterparts. Evidences indicate that they would perform key roles in the parasite metabolism such as nucleotide homeostasis, drug resistance, DNA damage responses and gene regulation, as well as host-parasite interactions, infection, virulence and immune evasion, placing them as attractive pharmacological targets.MAIN CONCLUSIONS NDPKs are very interesting multifunctional enzymes. In the present review, the potential of trypanosomatid NDPKs was highlighted, raising awareness of their value not only with respect to parasite biology but also as molecular targets.

show abstract

Structure, Folding and Stability of Nucleoside Diphosphate Kinases

Cited by 19 publications

References 88 publications

SalmonellaYqiC exerts its function through an oligomeric state

SalmonellaYqiC exerts its function through an oligomeric state

Revisiting Exome Data Identified Missed Splice Site Variant of the Asparagine Synthetase (ASNS) Gene

Revisiting trypanosomatid nucleoside diphosphate kinases

Contact Info

Product

Resources

About