Proteome-scale Analysis of Vertebrate Protein Thermoadaptation Modulated by Dynamic Allostery and Protein Solvation

Mapping Intimacies ◽

10.1101/2020.08.10.244558 ◽

2020 ◽

Author(s):

Zhen-lu Li ◽

Matthias Buck

Keyword(s):

Amino Acid ◽

Molecular Level ◽

Great Majority ◽

General Mechanism ◽

Homologous Proteins ◽

Proteome Level ◽

Lower Entropy ◽

Physical Features ◽

Vertebrate Protein ◽

Amino Acid Conservation

AbstractDespite large differences in behaviors and living conditions, vertebrate organisms share the great majority of proteins often with subtle differences in amino acid sequence. By comparing a set of substantially homologous proteins between model vertebrate organisms at a sub-proteome level, we discover a pattern of amino acid conservation and a shift in amino acid use, noticeably with an apparent distinction between homeotherms (warm-blooded species) and poikilotherms (cold-blooded species). Importantly, we establish a connection between the thermoadaptation of protein sequences manifest in the evolved proteins and two of their physical features: a change in their proteins dynamics and in their solvation. For poikilotherms such as frog and fish, the lower body temperature is expected to increase the association of proteins due to a decrease in protein dynamics and correspondingly lower entropy penalty on binding. In order to prevent overly-sticky protein association at low temperatures, we find that poikilotherms enhance the solvation of their proteins by favoring polar amino acids on their protein’s surface. This study unveils a general mechanism behind amino acid choices that constitute part of the thermoadaptation of vertebrate organisms at the molecular level.

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Diverse Mechanisms of Antimicrobial Activities of Lactoferrins, Lactoferricins, and Other Lactoferrin-Derived Peptides

International Journal of Molecular Sciences ◽

10.3390/ijms222011264 ◽

2021 ◽

Vol 22 (20) ◽

pp. 11264

Author(s):

Špela Gruden ◽

Nataša Poklar Ulrih

Keyword(s):

Antimicrobial Activity ◽

Amino Acid ◽

Amino Acid Composition ◽

Molecular Level ◽

Antioxidant Activities ◽

Antimicrobial Activities ◽

Iron Binding ◽

Primary Focus ◽

Binding Glycoprotein

Lactoferrins are an iron-binding glycoprotein that have important protective roles in the mammalian body through their numerous functions, which include antimicrobial, antitumor, anti-inflammatory, immunomodulatory, and antioxidant activities. Among these, their antimicrobial activity has been the most studied, although the mechanism behind antimicrobial activities remains to be elucidated. Thirty years ago, the first lactoferrin-derived peptide was isolated and showed higher antimicrobial activity than the native lactoferrin lactoferricin. Since then, numerous studies have investigated the antimicrobial potencies of lactoferrins, lactoferricins, and other lactoferrin-derived peptides to better understand their antimicrobial activities at the molecular level. This review defines the current antibacterial, antiviral, antifungal, and antiparasitic activities of lactoferrins, lactoferricins, and lactoferrin-derived peptides. The primary focus is on their different mechanisms of activity against bacteria, viruses, fungi, and parasites. The role of their structure, amino-acid composition, conformation, charge, hydrophobicity, and other factors that affect their mechanisms of antimicrobial activity are also reviewed.

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FIND: Identifying Functionally and Structurally Important Features in Protein Sequences with Deep Neural Networks

10.1101/592808 ◽

2019 ◽

Author(s):

Ranjani Murali ◽

James Hemp ◽

Victoria Orphan ◽

Yonatan Bisk

Keyword(s):

Neural Networks ◽

Amino Acid ◽

Hidden Markov Models ◽

Markov Models ◽

Genomic Sequence ◽

Hidden Markov ◽

Amino Acid Sequences ◽

Homologous Proteins ◽

Biological Studies ◽

Insight Into

AbstractThe ability to correctly predict the functional role of proteins from their amino acid sequences would significantly advance biological studies at the molecular level by improving our ability to understand the biochemical capability of biological organisms from their genomic sequence. Existing methods that are geared towards protein function prediction or annotation mostly use alignment-based approaches and probabilistic models such as Hidden-Markov Models. In this work we introduce a deep learning architecture (FunctionIdentification withNeuralDescriptions orFIND) which performs protein annotation from primary sequence. The accuracy of our methods matches state of the art techniques, such as protein classifiers based on Hidden Markov Models. Further, our approach allows for model introspection via a neural attention mechanism, which weights parts of the amino acid sequence proportionally to their relevance for functional assignment. In this way, the attention weights automatically uncover structurally and functionally relevant features of the classified protein and find novel functional motifs in previously uncharacterized proteins. While this model is applicable to any database of proteins, we chose to apply this model to superfamilies of homologous proteins, with the aim of extracting features inherent to divergent protein families within a larger superfamily. This provided insight into the functional diversification of an enzyme superfamily and its adaptation to different physiological contexts. We tested our approach on three families (nitrogenases, cytochromebd-type oxygen reductases and heme-copper oxygen reductases) and present a detailed analysis of the sequence characteristics identified in previously characterized proteins in the heme-copper oxygen reductase (HCO) superfamily. These are correlated with their catalytic relevance and evolutionary history. FIND was then applied to discover features in previously uncharacterized members of the HCO superfamily, providing insight into their unique sequence features. This modeling approach demonstrates the power of neural networks to recognize patterns in large datasets and can be utilized to discover biochemically and structurally important features in proteins from their amino acid sequences.Author summary

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Analysis of nucleotide substitutions and amino acid conservation in theDrosophila Adh genomic region

Genetica ◽

10.1007/bf01429217 ◽

1994 ◽

Vol 94 (1) ◽

pp. 27-36 ◽

Cited By ~ 5

Author(s):

R. Albalat ◽

G. Marfany ◽

R. Gonz�lez-Duarte

Keyword(s):

Amino Acid ◽

Genomic Region ◽

Nucleotide Substitutions ◽

Amino Acid Conservation

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Use of Amino Acid Environment-dependent Substitution Tables and Conformational Propensities in Structure Prediction from Aligned Sequences of Homologous Proteins. II. Secondary Structures

Journal of Molecular Biology ◽

10.1006/jmbi.1994.1330 ◽

1994 ◽

Vol 238 (5) ◽

pp. 693-708 ◽

Cited By ~ 31

Author(s):

Hiroshi Wako ◽

Tom L. Blundell

Keyword(s):

Amino Acid ◽

Structure Prediction ◽

Secondary Structures ◽

Homologous Proteins ◽

Acid Environment

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Use of Amino Acid Environment-dependent Substitution Tables and Conformational Propensities in Structure Prediction from Aligned Sequences of Homologous Proteins I. Solvent Accessibility Classes

Journal of Molecular Biology ◽

10.1006/jmbi.1994.1329 ◽

1994 ◽

Vol 238 (5) ◽

pp. 682-692 ◽

Cited By ~ 36

Author(s):

Hiroshi Wako ◽

Tom L. Blundell

Keyword(s):

Amino Acid ◽

Structure Prediction ◽

Solvent Accessibility ◽

Homologous Proteins ◽

Acid Environment

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Nucleotide and derived amino acid sequences of a cDNA coding for pre-uteroglobin from the lung of the hare (Lepus capensis)

Biochemical Journal ◽

10.1042/bj2350895 ◽

1986 ◽

Vol 235 (3) ◽

pp. 895-898 ◽

Cited By ~ 12

Author(s):

M S López de Haro ◽

A Nieto

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Nucleotide Sequence ◽

Amino Acid Sequence ◽

Amino Acid Sequences ◽

Untranslated Regions ◽

Coding Region ◽

Homologous Proteins ◽

Lepus Capensis ◽

Rabbit Gene

An almost full-length cDNA coding for pre-uteroglobin from hare lung was cloned and sequenced. The derived amino acid sequence indicated that hare pre-uteroglobin contained 91 amino acids, including a signal peptide of 21 residues. Comparison of the nucleotide sequence of hare pre-uteroglobin cDNA with that previously reported for the rabbit gene indicated five silent point substitutions and six others leading to amino acid changes in the coding region. The untranslated regions of both pre-uteroglobin mRNAs were very similar. The amino acid changes observed are discussed in relation to the different progesterone-binding abilities of both homologous proteins.

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The salivary transcriptome of Limnobdella mexicana (Annelida: Clitellata: Praobdellidae) and orthology determination of major leech anticoagulants

Parasitology ◽

10.1017/s0031182019000593 ◽

2019 ◽

Vol 146 (10) ◽

pp. 1338-1346

Author(s):

Rafael Iwama ◽

Alejandro Oceguera-Figueroa ◽

Gonzalo Giribet ◽

Sebastian Kvist

Keyword(s):

Amino Acid ◽

Positive Relationship ◽

Phylogenetic Analyses ◽

Factor Xa ◽

Amino Acid Conservation ◽

Inhibit Factor

AbstractBloodfeeding requires several adaptations that allow the parasite to feed efficiently. Leeches and other hematophagous animals have developed different mechanisms to inhibit hemostasis, one of the main barriers imposed by their hosts. Limnobdella mexicana is a member of the leech family Praobdellidae, a family of host generalists known for their preference to attach on mucosal membranes of mammals, such as those in nasopharyngeal cavities, bladders and ocular orbits. Previous studies have hypothesized a positive relationship between diversity of anticoagulants and diversity of hosts in bloodfeeding leeches. However, orthology determination of putative anticoagulants and the lack of standardization of sequencing effort and method hinder comparisons between publicly available transcriptomes generated in different laboratories. In the present study, we examine the first transcriptome of a praobdellid leech and identify 15 putative anticoagulants using a phylogeny-based inference approach, amino-acid conservation, Pfam domains and BLAST searches. Our phylogenetic analyses suggest that the ancestral leech was able to inhibit factor Xa and that some hirudins that have been reported in previous studies on leech anticoagulants may not be orthologous with the archetypal hirudin.

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Computer Simulation of Amino Acid Oligomerization in Aqueous Solutions Induced by Condensing Agent

Journal of Chemistry ◽

10.1155/2015/563065 ◽

2015 ◽

Vol 2015 ◽

pp. 1-6

Author(s):

Maxim Lubov ◽

Yuri Trushin ◽

Igor Eliseev ◽

Ivan Terterov ◽

Michael Dubina

Keyword(s):

Experimental Data ◽

Computer Simulation ◽

Amino Acid ◽

Aqueous Solutions ◽

Metal Ions ◽

Growth Model ◽

Physical Features ◽

Attachment Energy

Physical features of the amino acid oligomerization were studied. Growth model of the L-Glu monomer chain induced by the condensing agent in the aqueous solutions with and without metal ions was proposed. Computer simulation of oligomerization process was conducted and from the comparison of the calculated and experimental data attachment energy of the Leuchs anhydride of L-Glu to the oligomer was estimated.

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