scholarly journals Evolution of protein kinase substrate recognition at the active site

2018 ◽  
Author(s):  
David Bradley ◽  
Pedro Beltrao
Keyword(s):  
Protein Kinase ◽  
Sequence Variation ◽  
Common Ancestor ◽  
Last Common Ancestor ◽  
Kinase Substrate ◽  
Cellular Processes ◽  
Eukaryotic Species ◽  
Target Sites ◽  
Kinase Specificity ◽  
Substrate Motif

AbstractProtein kinases catalyse the phosphorylation of target proteins, controlling most cellular processes. The specificity of serine/threonine kinases is partly determined by interactions with a few residues near the phospho-acceptor residue, forming the so-called kinase substrate motif. Kinases have been extensively duplicated throughout evolution but little is known about when in time new target motifs have arisen. Here we show that sequence variation occurring early in the evolution of kinases is dominated by changes in specificity determining residues. We then analysed kinase specificity models, based on known target sites, observing that specificity has remained mostly unchanged for recent kinase duplications. Finally, analysis of phosphorylation data from a taxonomically broad set of 48 eukaryotic species indicates that most phosphorylation motifs are broadly distributed in eukaryotes but not present in prokaryotes. Overall, our results suggest that the set of eukaryotes kinase motifs present today was acquired soon after the eukaryotic last common ancestor and that early expansions of the protein kinase fold rapidly explored the space of possible target motifs.

scholarly journals Reprogramming protein kinase substrate specificity through synthetic mutations

2016 ◽  
Author(s):  
Joshua M. Lubner ◽  
George M. Church ◽  
Michael F. Chou ◽  
Daniel Schwartz
Keyword(s):  
Protein Kinase ◽  
Substrate Specificity ◽  
Structure Function ◽  
Binding Pocket ◽  
Missense Mutations ◽  
New Paradigm ◽  
Substrate Binding Pocket ◽  
Kinase Substrate ◽  
Substrate Preferences ◽  
Kinase Specificity

Protein kinase specificity is largely imparted through substrate binding pocket motifs. Missense mutations in these regions are frequently associated with human disease, and in some cases can alter substrate specificity. However, current efforts at decoding the influence of mutations on substrate specificity have been focused on disease-associated mutations. Here, we adapted the Proteomic Peptide Library (ProPeL) approach for determining kinase specificity to the task of exploring structure-function relationships in kinase specificity by interrogating the effects of synthetic mutation. We established a specificity model for the wild-type DYRK1A kinase with unprecedented resolution. Using existing crystallographic and sequence homology data, we rationally designed mutations that precisely reprogrammed the DYRK1A kinase at the P+1 position to mimic the substrate preferences of a related kinase, CK II. This study illustrates a new synthetic biological approach to reprogram kinase specificity by design, and a powerful new paradigm to investigate structure-function relationships underpinning kinase substrate specificity.

scholarly journals Activation of protein kinase C results in the displacement of its myristoylated, alanine-rich substrate from punctate structures in macrophage filopodia.

1990 ◽  
Vol 172 (4) ◽  
pp. 1211-1215 ◽  
Author(s):  
A Rosen ◽  
K F Keenan ◽  
M Thelen ◽  
A C Nairn ◽  
A Aderem
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Time Course ◽  
Phorbol Esters ◽  
Morphological Changes ◽  
Kinase Substrate ◽  
Cellular Processes ◽  
Kinase C ◽  
Membrane Cytoskeleton ◽  
Punctate Staining

The myristoylated, alanine-rich C kinase substrate (MARCKS) is a prominent substrate for protein kinase C (PKC) in a variety of cells, and has been implicated in diverse cellular processes including neurosecretion, fibroblast mitogenesis, and macrophage activation. In macrophages that have spread on the substratum, MARCKS has a punctate distribution at the cell-substratum interface of pseudopodia and filopodia. At these points, MARCKS co-localizes with vinculin and talin. Activation of PKC with phorbol esters results in the rapid disappearance of punctate staining of MARCKS, but not vinculin or talin, and is accompanied by cell spreading and loss of filopodia. The morphological changes and disappearance of punctate staining follow a time-course that closely approximates both the PKC-dependent phosphorylation of MARCKS, and its phosphorylation-dependent release from the plasma membrane. Our results suggest a role for PKC-dependent phosphorylation of MARCKS in the regulation of the membrane cytoskeleton.

scholarly journals Rice 3D chromatin structure correlates with sequence variation and meiotic recombination rate

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Agnieszka A. Golicz ◽  
Prem L. Bhalla ◽  
David Edwards ◽  
Mohan B. Singh
Keyword(s):  
Meiotic Recombination ◽  
Recombination Rate ◽  
Sequence Variation ◽  
Genome Structure ◽  
Rice Genome ◽  
Three Dimensional ◽  
3D Genome ◽  
Cellular Processes ◽  
Eukaryotic Species ◽  
Topologically Associated Domains

AbstractGenomes of many eukaryotic species have a defined three-dimensional architecture critical for cellular processes. They are partitioned into topologically associated domains (TADs), defined as regions of high chromatin inter-connectivity. While TADs are not a prominent feature of A. thaliana genome organization, they have been reported for other plants including rice, maize, tomato and cotton and for which TAD formation appears to be linked to transcription and chromatin epigenetic status. Here we show that in the rice genome, sequence variation and meiotic recombination rate correlate with the 3D genome structure. TADs display increased SNP and SV density and higher recombination rate compared to inter-TAD regions. We associate the observed differences with the TAD epigenetic landscape, TE composition and an increased incidence of meiotic crossovers.

scholarly journals Cytoskeletal architecture and its evolutionary significance in amoeboid eukaryotes and their mode of locomotion

2016 ◽  
Vol 3 (9) ◽  
pp. 160283 ◽  
Author(s):  
Yonas I. Tekle ◽  
Jessica R. Williams
Keyword(s):  
Common Ancestor ◽  
Granular Cell ◽  
Evolutionary Significance ◽  
Last Common Ancestor ◽  
Eukaryotic Evolution ◽  
Potential Significance ◽  
Origin And Evolution ◽  
Cellular Processes ◽  
Diverse Groups ◽  
First Time

The cytoskeleton is the hallmark of eukaryotic evolution. The molecular and architectural aspects of the cytoskeleton have been playing a prominent role in our understanding of the origin and evolution of eukaryotes. In this study, we seek to investigate the cytoskeleton architecture and its evolutionary significance in understudied amoeboid lineages belonging to Amoebozoa. These amoebae primarily use cytoplasmic extensions supported by the cytoskeleton to perform important cellular processes such as movement and feeding. Amoeboid structure has important taxonomic significance, but, owing to techniques used, its potential significance in understanding diversity of the group has been seriously compromised, leading to an under-appreciation of its value. Here, we used immunocytochemistry and confocal microscopy to study the architecture of microtubules (MTs) and F-actin in diverse groups of amoebae. Our results demonstrate that all Amoebozoa examined are characterized by a complex cytoskeletal array, unlike what has been previously thought to exist. Our results not only conclusively demonstrate that all amoebozoans possess complex cytoplasmic MTs, but also provide, for the first time, a potential synapomorphy for the molecularly defined Amoebozoa clade. Based on this evidence, the last common ancestor of amoebozoans is hypothesized to have had a complex interwoven MT architecture limited within the granular cell body. We also generate several cytoskeleton characters related to MT and F-actin, which are found to be robust for defining groups in deep and shallow nodes of Amoebozoa.

scholarly journals Experimental evidence for yawn contagion in orangutans (Pongo pygmaeus)

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Evy van Berlo ◽  
Alejandra P. Díaz-Loyo ◽  
Oscar E. Juárez-Mora ◽  
Mariska E. Kret ◽  
Jorg J. M. Massen
Keyword(s):  
Experimental Evidence ◽  
Common Ancestor ◽  
Great Apes ◽  
Pongo Pygmaeus ◽  
Last Common Ancestor ◽  
Contagious Yawning ◽  
Proximate Mechanism ◽  
Social Species ◽  
Ultimate Causation

AbstractYawning is highly contagious, yet both its proximate mechanism(s) and its ultimate causation remain poorly understood. Scholars have suggested a link between contagious yawning (CY) and sociality due to its appearance in mostly social species. Nevertheless, as findings are inconsistent, CY’s function and evolution remains heavily debated. One way to understand the evolution of CY is by studying it in hominids. Although CY has been found in chimpanzees and bonobos, but is absent in gorillas, data on orangutans are missing despite them being the least social hominid. Orangutans are thus interesting for understanding CY’s phylogeny. Here, we experimentally tested whether orangutans yawn contagiously in response to videos of conspecifics yawning. Furthermore, we investigated whether CY was affected by familiarity with the yawning individual (i.e. a familiar or unfamiliar conspecific and a 3D orangutan avatar). In 700 trials across 8 individuals, we found that orangutans are more likely to yawn in response to yawn videos compared to control videos of conspecifics, but not to yawn videos of the avatar. Interestingly, CY occurred regardless of whether a conspecific was familiar or unfamiliar. We conclude that CY was likely already present in the last common ancestor of humans and great apes, though more converging evidence is needed.

scholarly journals Cross-Predicting Essential Genes between Two Model Eukaryotic Species Using Machine Learning

2021 ◽  
Vol 22 (10) ◽  
pp. 5056
Author(s):  
Tulio L. Campos ◽  
Pasi K. Korhonen ◽  
Neil D. Young
Keyword(s):  
Machine Learning ◽  
Experimental Studies ◽  
Essential Genes ◽  
Subcellular Localisation ◽  
Cross Prediction ◽  
Gene Essentiality ◽  
C Elegans ◽  
Cellular Processes ◽  
Eukaryotic Species ◽  
The Cross

Experimental studies of Caenorhabditis elegans and Drosophila melanogaster have contributed substantially to our understanding of molecular and cellular processes in metazoans at large. Since the publication of their genomes, functional genomic investigations have identified genes that are essential or non-essential for survival in each species. Recently, a range of features linked to gene essentiality have been inferred using a machine learning (ML)-based approach, allowing essentiality predictions within a species. Nevertheless, predictions between species are still elusive. Here, we undertake a comprehensive study using ML to discover and validate features of essential genes common to both C. elegans and D. melanogaster. We demonstrate that the cross-species prediction of gene essentiality is possible using a subset of features linked to nucleotide/protein sequences, protein orthology and subcellular localisation, single-cell RNA-seq, and histone methylation markers. Complementary analyses showed that essential genes are enriched for transcription and translation functions and are preferentially located away from heterochromatin regions of C. elegans and D. melanogaster chromosomes. The present work should enable the cross-prediction of essential genes between model and non-model metazoans.

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