Inteins in Microbial Genomes: Distribution, Mechanism, and Function

Inteins are self-splicing protein elements (134 to 608 amino acids). Over 125 inteins have been cataloged in InBase, the on-line intein database (http://www.neb.com/neb/inteins.html), which includes the Intein Registry[1]. Inteins naturally present in pathogenic microbes represent novel, yet unexploited drug targets. Understanding the chemistry of the splicing reaction has allowed the manipulation of inteins, which are now used in many protein engineering applications[2].

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Protein engineering by chemical methods: Incorporation of nonnatural amino acids as a tool for studying protein folding, stability, and function

Peptide Science ◽

10.1002/pep2.24090 ◽

2018 ◽

Vol 110 (5) ◽

pp. e24090

Author(s):

Vincenzo De Filippis ◽

Nicola Pozzi ◽

Laura Acquasaliente ◽

Ilaria Artusi ◽

Giulia Pontarollo ◽

...

Keyword(s):

Amino Acids ◽

Protein Folding ◽

Protein Engineering ◽

Chemical Methods ◽

Nonnatural Amino Acids ◽

And Function

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Molecular characterization of SARS-CoV-2

Current Molecular Medicine ◽

10.2174/1566524020999201203213037 ◽

2020 ◽

Vol 20 ◽

Author(s):

Miribane Dërmaku-Sopjani ◽

Mentor Sopjani

Keyword(s):

Public Health ◽

Drug Targets ◽

Virus Genome ◽

Health Crisis ◽

Public Health Crisis ◽

Therapeutic Drugs ◽

New Public Health ◽

New Public ◽

And Function

Abstract:: The coronavirus disease 2019 (COVID-19) is currently a new public health crisis threatening the world. This pandemic disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus has been reported to be originated in bats and by yet unknown intermediary animals were transmitted to humans in China 2019. The SARSCoV- 2 spreads faster than its two ancestors the SARS-CoV and Middle East respiratory syndrome coronavirus (MERSCoV) but has reduced fatality. At present, the SARS-CoV-2 has caused about a 1.16 million of deaths with more than 43.4 million confirmed cases worldwide, resulting in a serious threat to public health globally with yet uncertain impact. The disease is transmitted by inhalation or direct contact with an infected person. The incubation period ranges from 1 to 14 days. COVID-19 is accompanied by various symptoms, including cough, fatigue. In most people the disease is mild, but in some other people, such as in elderly and people with chronic diseases, it may progress from pneumonia to a multi-organ dysfunction. Many people are reported asymptomatic. The virus genome is sequenced, but new variants are reported. Numerous biochemical aspects of its structure and function are revealed. To date, no clinically approved vaccines and/or specific therapeutic drugs are available to prevent or treat the COVID-19. However, there are reported intensive researches on the SARSCoV- 2 to potentially identify vaccines and/or drug targets, which may help to overcome the disease. In this review, we discuss recent advances in understanding the molecular structure of SARS-CoV-2 and its biochemical characteristics.

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The NALCN Channel Regulator UNC-80 Functions in a Subset of Interneurons To Regulate Caenorhabditis elegans Reversal Behavior

G3 Genes|Genome|Genetics ◽

10.1534/g3.119.400692 ◽

2019 ◽

Vol 10 (1) ◽

pp. 199-210 ◽

Cited By ~ 1

Author(s):

Chuanman Zhou ◽

Jintao Luo ◽

Xiaohui He ◽

Qian Zhou ◽

Yunxia He ◽

...

Keyword(s):

Plant Hormone ◽

Neuronal Excitability ◽

Resting Membrane Potential ◽

Loss Of Function ◽

Wild Type ◽

C Elegans ◽

Link Type ◽

Complex Functions ◽

And Function ◽

Multiple Loss

NALCN (Na+leak channel, non-selective) is a conserved, voltage-insensitive cation channel that regulates resting membrane potential and neuronal excitability. UNC79 and UNC80 are key regulators of the channel function. However, the behavioral effects of the channel complex are not entirely clear and the neurons in which the channel functions remain to be identified. In a forward genetic screen for C. elegans mutants with defective avoidance response to the plant hormone methyl salicylate (MeSa), we isolated multiple loss-of-function mutations in unc-80 and unc-79. C. elegans NALCN mutants exhibited similarly defective MeSa avoidance. Interestingly, NALCN, unc-80 and unc-79 mutants all showed wild type-like responses to other attractive or repelling odorants, suggesting that NALCN does not broadly affect odor detection or related forward and reversal behaviors. To understand in which neurons the channel functions, we determined the identities of a subset of unc-80-expressing neurons. We found that unc-79 and unc-80 are expressed and function in overlapping neurons, which verified previous assumptions. Neuron-specific transgene rescue and knockdown experiments suggest that the command interneurons AVA and AVE and the anterior guidepost neuron AVG can play a sufficient role in mediating unc-80 regulation of the MeSa avoidance. Though primarily based on genetic analyses, our results further imply that MeSa might activate NALCN by direct or indirect actions. Altogether, we provide an initial look into the key neurons in which the NALCN channel complex functions and identify a novel function of the channel in regulating C. elegans reversal behavior through command interneurons.

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Gill microbiome structure and function in the chemosymbiotic coastal lucinid Stewartia floridana

FEMS Microbiology Ecology ◽

10.1093/femsec/fiab042 ◽

2021 ◽

Author(s):

Shen Jean Lim ◽

Brenton Davis ◽

Danielle Gill ◽

John Swetenburg ◽

Laurie C Anderson ◽

...

Keyword(s):

Amino Acids ◽

Nutrient Cycling ◽

Bacterial Communities ◽

Structure And Function ◽

Differentially Expressed ◽

Seagrass Species ◽

Bare Sand ◽

And Function

Abstract Lucinid bivalves harbor environmentally acquired, chemosynthetic, gammaproteobacterial gill endosymbionts. Lucinid gill microbiomes, which may contain other gammaproteobacterial and/or spirochete taxa, remain under-sampled. To understand inter-host variability of the lucinid gill microbiome, specifically in the bacterial communities, we analyzed the microbiome content of Stewartia floridana collected from Florida. Sampled gills contained a monospecific gammaproteobacterial endosymbiont expressing lithoautotrophic, mixotrophic, diazotrophic, and C1 compound oxidation-related functions previously characterized in similar lucinid species. Another low-abundance Spirochaeta-like species in ∼72% of the sampled gills was most closely related to Spirochaeta-like species in another lucinid Phacoides pectinatus and formed a clade with known marine Spirochaeta symbionts. The spirochete expressed genes were involved in heterotrophy and the transport of sugars, amino acids, peptides, and other substrates. Few muscular and neurofilament genes from the host and none from the gammaproteobacterial and spirochete symbionts were differentially expressed among quadrats predominantly covered with seagrass species or 80% bare sand. Our results suggest that spirochetes are facultatively associated with S. floridana, with potential scavenging and nutrient cycling roles. Expressed stress- and defense-related functions in the host and symbionts also suggest species-species communications, which highlight the need for further study of the interactions among lucinid hosts, their microbiomes, and their environment.

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Cellular and metabolic mechanisms of nutrient actions in immune function

Nutrition and Diabetes ◽

10.1038/s41387-021-00162-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Philip Newsholme

Keyword(s):

Amino Acids ◽

Fatty Acids ◽

Vitamin D ◽

Immune System ◽

Cell Function ◽

Immune Cell ◽

Cell Structure ◽

Nutritional Intervention ◽

Immune Cell Function ◽

And Function

AbstractVarious nutrients can change cell structure, cellular metabolism, and cell function which is particularly important for cells of the immune system as nutrient availability is associated with the activation and function of diverse immune subsets. The most important nutrients for immune cell function and fate appear to be glucose, amino acids, fatty acids, and vitamin D. This perspective will describe recently published information describing the mechanism of action of prominent nutritional intervention agents where evidence exists as to their action and potency.

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Influence of spatial structure on protein damage susceptibility: a bioinformatics approach

Scientific Reports ◽

10.1038/s41598-021-84061-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Maximilian Fichtner ◽

Stefan Schuster ◽

Heiko Stark

Keyword(s):

Amino Acids ◽

Molecular Medicine ◽

Protein Damage ◽

Aging Research ◽

Form And Function ◽

The Core ◽

And Function ◽

Thermophilic Organisms ◽

Damage Susceptibility ◽

Protein Shell

AbstractAging research is a very popular field of research in which the deterioration or decline of various physiological features is studied. Here we consider the molecular level, which can also have effects on the macroscopic level. The proteinogenic amino acids differ in their susceptibilities to non-enzymatic modification. Some of these modifications can lead to protein damage and thus can affect the form and function of proteins. For this, it is important to know the distribution of amino acids between the protein shell/surface and the core. This was investigated in this study for all known structures of peptides and proteins available in the PDB. As a result, it is shown that the shell contains less susceptible amino acids than the core with the exception of thermophilic organisms. Furthermore, proteins could be classified according to their susceptibility. This can then be used in applications such as phylogeny, aging research, molecular medicine, and synthetic biology.

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Fielded applications of case-based reasoning

The Knowledge Engineering Review ◽

10.1017/s0269888906000580 ◽

2005 ◽

Vol 20 (3) ◽

pp. 321-323 ◽

Cited By ~ 8

Author(s):

WILLIAM CHEETHAM ◽

IAN WATSON

Keyword(s):

Case Based Reasoning ◽

Engineering Applications ◽

On Line ◽

Commercial Applications ◽

Case Based

This commentary describes notable commercial applications of case-based reasoning, including systems that have been in continuous profitable use for over a decade. It is divided into sections on engineering applications, helpdesk applications and on-line case-based reasoning.

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The proteome: structure, function and evolution

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2005.1802 ◽

2006 ◽

Vol 361 (1467) ◽

pp. 441-451 ◽

Cited By ~ 17

Author(s):

Keiran Fleming ◽

Lawrence A Kelley ◽

Suhail A Islam ◽

Robert M MacCallum ◽

Arne Muller ◽

...

Keyword(s):

Protein Function ◽

Sequence Similarity ◽

Structural Annotation ◽

New Approach ◽

Link Type ◽

University College London ◽

Automated Pipeline ◽

3D Genomics ◽

And Function ◽

Structural Homologue

This paper reports two studies to model the inter-relationships between protein sequence, structure and function. First, an automated pipeline to provide a structural annotation of proteomes in the major genomes is described. The results are stored in a database at Imperial College, London (3D-GENOMICS) that can be accessed at www.sbg.bio.ic.ac.uk . Analysis of the assignments to structural superfamilies provides evolutionary insights. 3D-GENOMICS is being integrated with related proteome annotation data at University College London and the European Bioinformatics Institute in a project known as e-protein ( http://www.e-protein.org/ ). The second topic is motivated by the developments in structural genomics projects in which the structure of a protein is determined prior to knowledge of its function. We have developed a new approach PHUNCTIONER that uses the gene ontology (GO) classification to supervise the extraction of the sequence signal responsible for protein function from a structure-based sequence alignment. Using GO we can obtain profiles for a range of specificities described in the ontology. In the region of low sequence similarity (around 15%), our method is more accurate than assignment from the closest structural homologue. The method is also able to identify the specific residues associated with the function of the protein family.

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