scholarly journals Molecular chaperones accelerate the evolution of their protein clients in yeast

2019 ◽  
Author(s):  
David Alvarez-Ponce ◽  
José Aguilar-Rodríguez ◽  
Mario A. Fares
Keyword(s):  
Protein Stability ◽  
Time Scales ◽  
Protein Evolution ◽  
Protein Interactions ◽  
Molecular Chaperones ◽  
Interaction Network ◽  
Evolutionary Divergence ◽  
Evolutionary Time ◽  
Genes Encoding ◽  
Shock Proteins

ABSTRACTProtein stability is a major constraint on protein evolution. Molecular chaperones, also known as heat-shock proteins, can relax this constraint and promote protein evolution by diminishing the deleterious effect of mutations on protein stability and folding. This effect, however, has only been stablished for a few chaperones. Here, we use a comprehensive chaperone-protein interaction network to study the effect of all yeast chaperones on the evolution of their protein substrates, that is, their clients. In particular, we analyze how yeast chaperones affect the evolutionary rates of their clients at two very different evolutionary time scales. We first study the effect of chaperone-mediated folding on protein evolution over the evolutionary divergence of Saccharomyces cerevisiae and S. paradoxus. We then test whether yeast chaperones have left a similar signature on the patterns of standing genetic variation found in modern wild and domesticated strains of S. cerevisiae. We find that genes encoding chaperone clients have diverged faster than genes encoding nonclient proteins when controlling for their number of protein-protein interactions. We also find that genes encoding client proteins have accumulated more intra-specific genetic diversity than those encoding nonclient proteins. In a number of multivariate analyses, controlling by other well-known factors that affect protein evolution, we find that chaperone dependence explains the largest fraction of the observed variance in the rate of evolution at both evolutionary time scales. Chaperones affecting rates of protein evolution mostly belong to two major chaperone families: Hsp70s and Hsp90s. Our analyses show that protein chaperones, by virtue of their ability to buffer destabilizing mutations and their role in modulating protein genotype-phenotype maps, have a considerable accelerating effect on protein evolution.

scholarly journals Molecular Chaperones Accelerate the Evolution of Their Protein Clients in Yeast

2019 ◽  
Vol 11 (8) ◽  
pp. 2360-2375 ◽  
Author(s):  
David Alvarez-Ponce ◽  
José Aguilar-Rodríguez ◽  
Mario A Fares
Keyword(s):  
Protein Stability ◽  
Time Scales ◽  
Protein Evolution ◽  
Protein Interactions ◽  
Molecular Chaperones ◽  
Interaction Network ◽  
Evolutionary Divergence ◽  
Evolutionary Time ◽  
Genes Encoding ◽  
Client Proteins

Abstract Protein stability is a major constraint on protein evolution. Molecular chaperones, also known as heat-shock proteins, can relax this constraint and promote protein evolution by diminishing the deleterious effect of mutations on protein stability and folding. This effect, however, has only been stablished for a few chaperones. Here, we use a comprehensive chaperone–protein interaction network to study the effect of all yeast chaperones on the evolution of their protein substrates, that is, their clients. In particular, we analyze how yeast chaperones affect the evolutionary rates of their clients at two very different evolutionary time scales. We first study the effect of chaperone-mediated folding on protein evolution over the evolutionary divergence of Saccharomyces cerevisiae and S. paradoxus. We then test whether yeast chaperones have left a similar signature on the patterns of standing genetic variation found in modern wild and domesticated strains of S. cerevisiae. We find that genes encoding chaperone clients have diverged faster than genes encoding non-client proteins when controlling for their number of protein–protein interactions. We also find that genes encoding client proteins have accumulated more intraspecific genetic diversity than those encoding non-client proteins. In a number of multivariate analyses, controlling by other well-known factors that affect protein evolution, we find that chaperone dependence explains the largest fraction of the observed variance in the rate of evolution at both evolutionary time scales. Chaperones affecting rates of protein evolution mostly belong to two major chaperone families: Hsp70s and Hsp90s. Our analyses show that protein chaperones, by virtue of their ability to buffer destabilizing mutations and their role in modulating protein genotype–phenotype maps, have a considerable accelerating effect on protein evolution.

scholarly journals The molecular chaperone DnaK accelerates protein evolution

2016 ◽  
Author(s):  
Jose Aguilar-Rodriguez ◽  
Beatriz Sabater-Munoz ◽  
Victor Berlanga ◽  
David Alvarez-Ponce ◽  
Andreas Wagner ◽  
...  
Keyword(s):  
Time Scales ◽  
Protein Evolution ◽  
Sequence Data ◽  
Evolutionary Rates ◽  
Evolutionary Time ◽  
Nucleotide Substitutions ◽  
Chaperone Dnak ◽  
Nucleotide Insertions ◽  
Shock Proteins ◽  
And Function

Molecular chaperones, also known as heat-shock proteins, refold misfolded proteins and help other proteins reach their native conformation. Thanks to these abilities, some chaperones, such as the Hsp90 protein or the chaperonin GroEL, can buffer the deleterious phenotypic effects of mutations that alter protein structure and function. Hsp70 chaperones use a chaperoning mechanism different from Hsp90 and GroEL, and it is not known whether they can also buffer mutations. Here, we show that they can. To this end, we performed a mutation accumulation experiment inEscherichia coli, followed by whole-genome resequencing. Our sequence data shows that overexpression of the Hsp70 chaperone DnaK increases the tolerance of its clients for nonsynonymous nucleotide substitutions and nucleotide insertions and deletions. We also show that this elevated mutational buffering on short evolutionary time scales translates into differences in evolutionary rates on intermediate and long evolutionary time scales. To this end, we compared the evolutionary rates of DnaK clients and nonclients using the genomes ofE. coli,Salmonella typhimurium, and 83 other gamma-proteobacterial species. We find that clients that interact strongly with DnaK evolve faster than weakly interacting clients. Our results imply that all three major chaperone classes can buffer mutations and affect protein evolution. They illustrate how an individual protein like a chaperone can have a disproportionate effect on proteome evolution.

scholarly journals Evolution of frustrated and stabilising contacts in reconstructed ancient proteins

2021 ◽  
Author(s):  
Martina Crippa ◽  
Damiano Andreghetti ◽  
Riccardo Capelli ◽  
Guido Tiana
Keyword(s):  
Amino Acids ◽  
Protein Stability ◽  
Interaction Network ◽  
Reconstruction Algorithm ◽  
Major Determinant ◽  
Evolutionary Time ◽  
Energetic Properties ◽  
Ancient Proteins ◽  
Evolutionary Fitness

AbstractEnergetic properties of a protein are a major determinant of its evolutionary fitness. Using a reconstruction algorithm, dating the reconstructed proteins and calculating the interaction network between their amino acids through a coevolutionary approach, we studied how the interactions that stabilise 890 proteins, belonging to five families, evolved for billions of years. In particular, we focused our attention on the network of most strongly attractive contacts and on that of poorly optimised, frustrated contacts. Our results support the idea that the cluster of most attractive interactions extends its size along evolutionary time, but from the data, we cannot conclude that protein stability or that the degree of frustration tends always to decrease.

scholarly journals Bradyrhizobium diazoefficiens USDA 110-Glycine max interactome provides candidate proteins associated with symbiosis

2018 ◽  
Author(s):  
Li Zhang ◽  
Jin-Yang Liu ◽  
Huan Gu ◽  
Yanfang Du ◽  
Jian-Fang Zuo ◽  
...  
Keyword(s):  
Glycine Max ◽  
Protein Interactions ◽  
Interaction Network ◽  
Snare Proteins ◽  
Protein Protein Interactions ◽  
Bacterial Proteins ◽  
Dicarboxylate Transport ◽  
Protein Interactome ◽  
Subnetwork Analysis ◽  
Shock Proteins

AbstractAlthough the legume-rhizobium symbiosis is a most important biological process, there is a limited knowledge about the protein interaction network between host and symbiont. Using interolog and domain-based approaches, we constructed an inter-species protein interactome with 5115 protein-protein interactions between 2291 Glycine max and 290 Bradyrhizobium diazoefficiens USDA 110 proteins. The interactome was validated by expression pattern analysis in nodules, GO term semantic similarity, and co-expression analysis. One sub-network was further confirmed using luciferase complementation image assay. In the G. max-B. diazoefficiens interactome, bacterial proteins are mainly ion channel and transporters of carbohydrates and cations, while G. max proteins are mainly involved in the processes of metabolism, signal transduction, and transport. We also identified the top ten highly interacting proteins (hubs) for each of the two species. KEGG pathway analysis for each hub showed that two 14-3-3 proteins (SGF14g and SGF14k) and five heat shock proteins in G. max are possibly involved in symbiosis, and ten hubs in B. diazoefficiens may be important symbiotic effectors. Subnetwork analysis showed that 18 symbiosis-related SNARE proteins may play roles in regulating bacterial ion channels, and SGF14g and SGF14k possibly regulate the rhizobium dicarboxylate transport protein DctA. The predicted interactome and symbiosis proteins provide a valuable basis for understanding the molecular mechanism of root nodule symbiosis in soybean.

scholarly journals Insights Into Heat Response Mechanisms in Clematis Species: Physiological Analysis, Expression Profiles and Function Verification

2021 ◽  
Author(s):  
Hao Zhang ◽  
Changhua Jiang ◽  
Rui Wang ◽  
Long Zhang ◽  
Ruonan Gai ◽  
...  
Keyword(s):  
Heat Stress ◽  
Heat Shock ◽  
Expression Profiles ◽  
Interaction Network ◽  
Differentially Expressed ◽  
Genes Encoding ◽  
Heat Response ◽  
Physiological Analysis ◽  
Japanese Gardens ◽  
Shock Proteins

Abstract Clematis species are commonly grown in western and Japanese gardens. Heat stress can inhibit many physiological processes mediating plant growth and development. The mechanism regulating responses to heat has been well characterized in Arabidopsis thaliana and some crops, but not in horticultural plants, including Clematis species. In this study, we found that Clematis alpina ‘Stolwijk Gold’ was heat-sensitive whereas Clematis vitalba and Clematis viticella ‘Polish Spirit’ were heat-tolerant based on the physiological analyses in heat stress. Transcriptomic profiling identified a set of heat tolerance-related genes (HTGs). Consistent with the observed phenotype in heat stress, 41.43% of the differentially expressed HTGs between heat treatment and control were down-regulated in heat-sensitive cultivar Stolwijk Gold, but only 9.80% and 20.79% of the differentially expressed HTGs in heat resistant C. vitalba and Polish Spirit, respectively. Co-expression network, protein–protein interaction network and phylogenetic analysis revealed that the genes encoding heat shock transcription factors (HSFs) and heat shock proteins (HSPs) played an essential role in Clematis resistance to heat stress. Ultimately, we proposed that two clades of HSFs may have diverse functions in regulating heat resistance from C. vitalba and CvHSFA2-2 could endow different host with high temperature resistance. This study provides first insights into the diversity of the heat response mechanisms among Clematis species.

scholarly journals Transcriptional Modulation of Heat-Shock Protein Gene Expression

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Anastasis Stephanou ◽  
David S. Latchman
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Heat Shock ◽  
Molecular Chaperones ◽  
Protein Gene ◽  
Genes Encoding ◽  
Transcriptional Modulation ◽  
Shock Proteins ◽  
Complex Signaling ◽  
Novel Therapeutic

Heat-shock proteins (Hsps) are molecular chaperones that are ubiquitously expressed but are also induced in cells exposed to stressful stimuli. Hsps have been implicated in the induction and propagation of several diseases. This paper focuses on regulatory factors that control the transcription of the genes encoding Hsps. We also highlight how distinct transcription factors are able to interact and modulate Hsps in different pathological states. Thus, a better understanding of the complex signaling pathways regulating Hsp expression may lead to novel therapeutic targets.

scholarly journals Cyanobacterial heat-shock response: role and regulation of molecular chaperones

Microbiology ◽  
2014 ◽  
Vol 160 (4) ◽  
pp. 647-658 ◽  
Author(s):  
Hema Rajaram ◽  
Akhilesh Kumar Chaurasia ◽  
Shree Kumar Apte
Keyword(s):  
Heat Shock ◽  
Molecular Chaperones ◽  
Heat Shock Response ◽  
Ecological Niches ◽  
Nitrogen Fixing ◽  
Shock Response ◽  
Genes Encoding ◽  
Small Hsps ◽  
Shock Proteins

Cyanobacteria constitute a morphologically diverse group of oxygenic photoautotrophic microbes which range from unicellular to multicellular, and non-nitrogen-fixing to nitrogen-fixing types. Sustained long-term exposure to changing environmental conditions, during their three billion years of evolution, has presumably led to their adaptation to diverse ecological niches. The ability to maintain protein conformational homeostasis (folding–misfolding–refolding or aggregation–degradation) by molecular chaperones holds the key to the stress adaptability of cyanobacteria. Although cyanobacteria possess several genes encoding DnaK and DnaJ family proteins, these are not the most abundant heat-shock proteins (Hsps), as is the case in other bacteria. Instead, the Hsp60 family of proteins, comprising two phylogenetically conserved proteins, and small Hsps are more abundant during heat stress. The contribution of the Hsp100 (ClpB) family of proteins and of small Hsps in the unicellular cyanobacteria (Synechocystis and Synechococcus) as well as that of Hsp60 proteins in the filamentous cyanobacteria (Anabaena) to thermotolerance has been elucidated. The regulation of chaperone genes by several cis-elements and trans-acting factors has also been well documented. Recent studies have demonstrated novel transcriptional and translational (mRNA secondary structure) regulatory mechanisms in unicellular cyanobacteria. This article provides an insight into the heat-shock response: its organization, and ecophysiological regulation and role of molecular chaperones, in unicellular and filamentous nitrogen-fixing cyanobacterial strains.

Network Pharmacology Approach uncovering Pathways involved in targeting Hsp90 through Curcumin and Epigallocatechin to control Inflammation.

2019 ◽  
Vol 16 ◽  
Author(s):  
Umme Hani ◽  
Shivananda Kandagalla ◽  
B.S. Sharath ◽  
K Jyothsna. ◽  
H Manjunatha.
Keyword(s):  
Gene Ontology ◽  
Molecular Chaperones ◽  
Curcuma Longa ◽  
Interaction Network ◽  
Network Pharmacology ◽  
Heme Oxygenase 1 ◽  
Nrf2 Pathway ◽  
Functional Behavior ◽  
Inflammatory Proteins ◽  
Prime Target

: Hsp90 are molecular chaperones of chronic inflammatory proteins and have emerged as prime target for treatment of inflammation. Principal components from Curcuma longa and Camellia sinensis, Curcumin and EGC respectively possesses anti-inflammatory properties inhibiting cytokines responsible for inflammation. Both act on common pathways in upregulation of heme oxygenase 1 through Pkcδ-Nrf2 pathway and downregulation of Tlr4, which in turn suppress expression of Hsp90. Curcumin and EGC were also found to bind -N and -C terminal domain of Hsp90 respectively. Based on this, work was designed with network pharmacological approach. Hsp90 associated gene targets of Curcumin and EGC were collected from databases, and gene ontology studies were done. PPI were obtained from string database for specific genes involved in Pkcδ-Nrf2 and Tlr4 pathway. Protein interaction network was constructed by cytoscape, and networks of Hsp90, Curcumin and EGC were merged to get common genes involved in Pkcδ-Nrf2 and Tlr4 pathway. Cluego analysis was done for obtained common genes to identify functional behavior in human diseases. Main proteins involved were identified as key regulators in Pkcδ-Nrf2 and Tlr4 pathway for controlling expression of Hsp90 from Curcumin and EGC in inflammation. Docking was performed on main proteins, Hsp90, Pkcδ and Tlr4 with Curcumin and EGC, significant binding energy was obtained for docked complexes. Combinatorial effects of Curcumin and EGC were observed in Pkcδ-Nrf2 and Tlr4pathway. Present study is an attempt to unravel common pathways mediated in intervention of Curcumin and EGC for suppression of Hsp90 associated with inflammation.

scholarly journals Short loop functional commonality identified in leukaemia proteome highlights crucial protein sub-networks

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Sun Sook Chung ◽  
Joseph C F Ng ◽  
Anna Laddach ◽  
N Shaun B Thomas ◽  
Franca Fraternali
Keyword(s):  
Protein Interactions ◽  
Large Scale ◽  
Interaction Network ◽  
Protein Protein Interactions ◽  
Protein Protein Interaction ◽  
Ppi Networks ◽  
Short Loop ◽  
New Strategy ◽  
Loop Network ◽  
Protein Protein Interaction Network

Abstract Direct drug targeting of mutated proteins in cancer is not always possible and efficacy can be nullified by compensating protein–protein interactions (PPIs). Here, we establish an in silico pipeline to identify specific PPI sub-networks containing mutated proteins as potential targets, which we apply to mutation data of four different leukaemias. Our method is based on extracting cyclic interactions of a small number of proteins topologically and functionally linked in the Protein–Protein Interaction Network (PPIN), which we call short loop network motifs (SLM). We uncover a new property of PPINs named ‘short loop commonality’ to measure indirect PPIs occurring via common SLM interactions. This detects ‘modules’ of PPI networks enriched with annotated biological functions of proteins containing mutation hotspots, exemplified by FLT3 and other receptor tyrosine kinase proteins. We further identify functional dependency or mutual exclusivity of short loop commonality pairs in large-scale cellular CRISPR–Cas9 knockout screening data. Our pipeline provides a new strategy for identifying new therapeutic targets for drug discovery.

scholarly journals A unified resource and configurable model of the synapse proteome and its role in disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Oksana Sorokina ◽  
Colin Mclean ◽  
Mike D. R. Croning ◽  
Katharina F. Heil ◽  
Emilia Wysocka ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Synaptic Proteins ◽  
Protein Protein Interactions ◽  
Network Resource ◽  
Unique Protein ◽  
Co Morbidity ◽  
Genes Encoding ◽  
Protein Components ◽  
Accessible Format ◽  
Neuronal Disorders

AbstractGenes encoding synaptic proteins are highly associated with neuronal disorders many of which show clinical co-morbidity. We integrated 58 published synaptic proteomic datasets that describe over 8000 proteins and combined them with direct protein–protein interactions and functional metadata to build a network resource that reveals the shared and unique protein components that underpin multiple disorders. All the data are provided in a flexible and accessible format to encourage custom use.

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