scholarly journals Phospho-islands and the evolution of phosphorylated amino acids in mammals

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10436
Author(s):  
Mikhail Moldovan ◽  
Mikhail S. Gelfand
Keyword(s):  
Amino Acids ◽  
Protein Function ◽  
Chemical Properties ◽  
Evolutionary Analysis ◽  
Post Translational Modification ◽  
Evolutionary Patterns ◽  
Charged Amino Acids ◽  
Physico Chemical ◽  
Frequent Mutations ◽  
Evolutionary Aspects

Background Protein phosphorylation is the best studied post-translational modification strongly influencing protein function. Phosphorylated amino acids not only differ in physico-chemical properties from non-phosphorylated counterparts, but also exhibit different evolutionary patterns, tending to mutate to and originate from negatively charged amino acids (NCAs). The distribution of phosphosites along protein sequences is non-uniform, as phosphosites tend to cluster, forming so-called phospho-islands. Methods Here, we have developed a hidden Markov model-based procedure for the identification of phospho-islands and studied the properties of the obtained phosphorylation clusters. To check robustness of evolutionary analysis, we consider different models for the reconstructions of ancestral phosphorylation states. Results Clustered phosphosites differ from individual phosphosites in several functional and evolutionary aspects including underrepresentation of phosphotyrosines, higher conservation, more frequent mutations to NCAs. The spectrum of tissues, frequencies of specific phosphorylation contexts, and mutational patterns observed near clustered sites also are different.

scholarly journals Phospho-islands and the evolution of phosphorylated amino acids in mammals

2020 ◽  
Author(s):  
Mikhail A. Moldovan ◽  
Mikhail S. Gelfand
Keyword(s):  
Amino Acids ◽  
Protein Function ◽  
Chemical Properties ◽  
Evolutionary Analysis ◽  
Post Translational Modification ◽  
Evolutionary Patterns ◽  
Charged Amino Acids ◽  
Physico Chemical ◽  
Frequent Mutations ◽  
Evolutionary Aspects

AbstractBackgroundProtein phosphorylation is the best studied post-translational modification strongly influencing protein function. Phosphorylated amino acids not only differ in physico-chemical properties from non-phosphorylated counterparts, but also exhibit different evolutionary patterns, tending to mutate to and originate from negatively charged amino acids. The distribution of phosphosites along protein sequences is non-uniform, as phosphosites tend to cluster, forming so-called phospho-islands.MethodsHere, we have developed an HMM-based procedure for the identification of phospho-islands and studied the properties of the obtained phosphorylation clusters. To check robustness of evolutionary analysis, we consider different models for the reconstructions of ancestral phosphorylation states.ResultsClustered phosphosites differ from individual phosphosites in several functional and evolutionary aspects including underrepresentation of phosphotyrosines, higher conservation, more frequent mutations to negatively charged amino acids. The spectrum of tissues, frequencies of specific phosphorylation contexts, and mutational patterns observed near clustered sites also are different.

scholarly journals Identification of 4 charged amino acids essential for Slc4a10 ‐derived protein function

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Helle Hasager Damkier ◽  
Christian Aalkjaer ◽  
Jeppe Praetorius
Keyword(s):  
Amino Acids ◽  
Protein Function ◽  
Charged Amino Acids

scholarly journals Porin from Marine Bacterium Marinomonas primoryensis KMM 3633T: Isolation, Physico-Chemical Properties, and Functional Activity

Molecules ◽  
2020 ◽  
Vol 25 (14) ◽  
pp. 3131
Author(s):  
Olga D. Novikova ◽  
Valentina A. Khomenko ◽  
Natalia Yu. Kim ◽  
Galina N. Likhatskaya ◽  
Lyudmila A. Romanenko ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Lipid Membranes ◽  
Marine Bacterium ◽  
Chemical Properties ◽  
Cell Permeability ◽  
Oligomeric Structure ◽  
Black Lipid Membranes ◽  
Physico Chemical ◽  
Coastal Sea

Marinomonas primoryensis KMM 3633T, extreme living marine bacterium was isolated from a sample of coastal sea ice in the Amursky Bay near Vladivostok, Russia. The goal of our investigation is to study outer membrane channels determining cell permeability. Porin from M. primoryensis KMM 3633T (MpOmp) has been isolated and characterized. Amino acid analysis and whole genome sequencing were the sources of amino acid data of porin, identified as Porin_4 according to the conservative domain searching. The amino acid composition of MpOmp distinguished by high content of acidic amino acids and low content of sulfur-containing amino acids, but there are no tryptophan residues in its molecule. The native MpOmp existed as a trimer. The reconstitution of MpOmp into black lipid membranes demonstrated its ability to form ion channels whose conductivity depends on the electrolyte concentration. The spatial structure of MpOmp had features typical for the classical gram-negative porins. However, the oligomeric structure of isolated MpOmp was distinguished by very low stability: heat-modified monomer was already observed at 30 °C. The data obtained suggest the stabilizing role of lipids in the natural membrane of marine bacteria in the formation of the oligomeric structure of porin.

scholarly journals Negatively charged amino acids in the stalk region of membrane proteins reduce ectodomain shedding

2020 ◽  
Vol 295 (35) ◽  
pp. 12343-12352 ◽  
Author(s):  
Ryo Iwagishi ◽  
Rika Tanaka ◽  
Munenosuke Seto ◽  
Tomoyo Takagi ◽  
Naoko Norioka ◽  
...  
Keyword(s):  
Amino Acids ◽  
Membrane Proteins ◽  
Molecular Mechanisms ◽  
Alternative Exon ◽  
Ectodomain Shedding ◽  
Post Translational Modification ◽  
Charged Amino Acids ◽  
Juxtamembrane Region ◽  
Protein Variants ◽  
Variant Protein

Ectodomain shedding is a post-translational modification mechanism by which the entire extracellular domain of membrane proteins is liberated through juxtamembrane processing. Because shedding rapidly and irreversibly alters the characteristics of cells, this process is properly regulated. However, the molecular mechanisms governing the propensity of membrane proteins to shedding are largely unknown. Here, we present evidence that negatively charged amino acids within the stalk region, an unstructured juxtamembrane region at which shedding occurs, contribute to shedding susceptibility. We show that two activated leukocyte cell adhesion molecule (ALCAM) protein variants produced by alternative splicing have different susceptibilities to ADAM metallopeptidase domain 17 (ADAM17)-mediated shedding. Of note, the inclusion of a stalk region encoded by a 39-bp-long alternative exon conferred shedding resistance. We found that this alternative exon encodes a large proportion of negatively charged amino acids, which we demonstrate are indispensable for conferring the shedding resistance. We also show that the introduction of negatively charged amino acids into the stalk region of shedding-susceptible ALCAM variant protein attenuates its shedding. Furthermore, we observed that negatively charged amino acids residing in the stalk region of Erb-B2 receptor tyrosine kinase 4 (ERBB4) are indispensable for its shedding resistance. Collectively, our results indicate that negatively charged amino acids within the stalk region interfere with the shedding of multiple membrane proteins. We conclude that the composition of the stalk region determines the shedding susceptibility of membrane proteins.

scholarly journals iDPGK: characterization and identification of lysine phosphoglycerylation sites based on sequence-based features

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Kai-Yao Huang ◽  
Fang-Yu Hung ◽  
Hui-Ju Kao ◽  
Hui-Hsuan Lau ◽  
Shun-Long Weng
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Training Dataset ◽  
Post Translational Modification ◽  
Web Based ◽  
Charged Amino Acids ◽  
Pair Composition ◽  
Weighted Matrix ◽  
Svm Model ◽  
Effective Performance

Abstract Background Protein phosphoglycerylation, the addition of a 1,3-bisphosphoglyceric acid (1,3-BPG) to a lysine residue of a protein and thus to form a 3-phosphoglyceryl-lysine, is a reversible and non-enzymatic post-translational modification (PTM) and plays a regulatory role in glucose metabolism and glycolytic process. As the number of experimentally verified phosphoglycerylated sites has increased significantly, statistical or machine learning methods are imperative for investigating the characteristics of phosphoglycerylation sites. Currently, research into phosphoglycerylation is very limited, and only a few resources are available for the computational identification of phosphoglycerylation sites. Result We present a bioinformatics investigation of phosphoglycerylation sites based on sequence-based features. The TwoSampleLogo analysis reveals that the regions surrounding the phosphoglycerylation sites contain a high relatively of positively charged amino acids, especially in the upstream flanking region. Additionally, the non-polar and aliphatic amino acids are more abundant surrounding phosphoglycerylated lysine following the results of PTM-Logo, which may play a functional role in discriminating between phosphoglycerylation and non-phosphoglycerylation sites. Many types of features were adopted to build the prediction model on the training dataset, including amino acid composition, amino acid pair composition, positional weighted matrix and position-specific scoring matrix. Further, to improve the predictive power, numerous top features ranked by F-score were considered as the final combination for classification, and thus the predictive models were trained using DT, RF and SVM classifiers. Evaluation by five-fold cross-validation showed that the selected features was most effective in discriminating between phosphoglycerylated and non-phosphoglycerylated sites. Conclusion The SVM model trained with the selected sequence-based features performed well, with a sensitivity of 77.5%, a specificity of 73.6%, an accuracy of 74.9%, and a Matthews Correlation Coefficient value of 0.49. Furthermore, the model also consistently provides the effective performance in independent testing set, yielding sensitivity of 75.7% and specificity of 64.9%. Finally, the model has been implemented as a web-based system, namely iDPGK, which is now freely available at http://mer.hc.mmh.org.tw/iDPGK/.

scholarly journals Hydrophobicity Revisited: a Molecular Story

2020 ◽  
Author(s):  
David Cavanaugh ◽  
Krishnan Chittur
Keyword(s):  
Amino Acids ◽  
Free Energy ◽  
Amino Acid ◽  
Linear Regression ◽  
Group Structure ◽  
Chemical Properties ◽  
Molecular Geometry ◽  
Superior Performance ◽  
Acid Property ◽  
Physico Chemical

In a previous paper we have introduced a new hydrophobicity proclivity scale and justified its superior performance characteristics, particularly in the context of a scale for protein alignments, but also for its strong correlation with many other amino-acid physico-chemical properties. Within that paper, we calculated a corrected free energy of residue burial of each amino-acid in folded proteins from a linear regression of amino-acid free energy of transfer from water to n-Octanol (F&P octanol scale dGow, Y axis) and our Hydrophobicity Proclivity Scale<br>(HPS, X axis). In this present paper we pursue the latter general findings in more detail by considering the relationship of hydrophobicity and other physico-amino-<br>acid scales with the molecular geometry of amino-acids and secondary group structure/surface chemistry, with a concommitant discussion of the dimensions/geometry<br>of the caveties that amino-acids make in water. We identify a series of molecular physico-chemical properties that uniquely define the natural selection and geometry of the 20 natural amino-acids. We use the corrected free energy of amino-acid burials in proteins (Y axis) and a multiple linear regression to identify the AA molecular physico-chemical properties (X1, X2, ...) that explain the energetics of amino-<br>acid water contacts in an unfolded protein state to that of the folded protein state by modeling these two states as a solvent-solvent transfer, thus, providing a thermodynamical model for the initial stages of protein folding. Between our previous paper and the current paper we can greatly simplify and reduce the very large number of amino-acid scales in the literature to a small number of amino-acid property scales. Finally, we explore the numerical relationship between the structure of the genetic code and molecular physico-chemical properties of AA’s that in turn can be related directly to hydrophobicity. We validate and explain our novel models we describe herein with extensive data from the literature.<br>

scholarly journals Exploring amino acid functions in a deep mutational landscape

2020 ◽  
Author(s):  
Alistair Dunham ◽  
Pedro Beltrao
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Clustering Analysis ◽  
Chemical Properties ◽  
Diverse Range ◽  
Mutational Landscape ◽  
Charged Amino Acids ◽  
Large Numbers ◽  
Recent Developments ◽  
And Chemical Properties

AbstractAmino acids fulfil a diverse range of roles in proteins, each utilising its chemical properties in different ways in different contexts to create required functions. For example, cysteines form disulphide or hydrogen bonds in different circumstances and charged amino acids do not always make use of their charge. The repertoire of amino acid functions and the frequency at which they occur in proteins remains understudied. Measuring large numbers of mutational consequences, which can elucidate the role an amino acid plays, was prohibitively time consuming until recent developments in deep mutational scanning. In this study we gathered data from 28 deep mutational scanning studies, covering 6291 positions in 30 proteins, and used the consequences of mutation at each position to define a mutational landscape. We demonstrated rich relationships between this landscape and biophysical or evolutionary properties. Finally, we identified 100 functional amino acid subtypes with a data-driven clustering analysis and studied their features, including their frequencies and chemical properties such as tolerating polarity, hydrophobicity or being intolerant of charge or specific amino acids. The mutational landscape and amino acid subtypes provide a foundational catalogue of amino acid functional diversity, which will be refined as the number of studied protein positions increases.

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