Turkey and chicken interferon-γ, which share high sequence identity, are biologically cross-reactive

In this paper we report on the isolation and characterization, for the first time, of a complete 6511 bp retrotransposon of sunflower. Considering its protein domain order and sequence similarity to other copia elements of dicotyledons, this retrotransposon was assigned to the copia retrotransposon superfamily and named HACRE1 ( Helianthus annuus copia-like retroelement 1). HACRE1 carries 5′ and 3′ long terminal repeats (LTRs) flanking an internal region of 4661 bp. The LTRs are identical in their sequence except for two deletions of 7 and 5 nucleotides in the 5′ LTR. Based on the sequence identity of the LTRs, HACRE1 was estimated to have inserted within the last ∼84 000 years. The isolated sequence contains a complete open reading frame with only one complete reading frame. The absence of nonsense mutations agrees with the very high sequence identity between LTRs, confirming that HACRE1 insertion is recent. The haploid genome of sunflower (inbred line HCM) contains about 160 copies of HACRE1. This retrotransposon is expressed in leaflets from 7-day-old plantlets under different light conditions, probably in relation to the occurrence of many putative light-related regulatory cis-elements in the LTRs. However, sequenced cDNAs show less variability than HACRE1 genomic sequences, indicating that only a subset of this family is expressed under these conditions.

Download Full-text

Structure-based group A streptococcal vaccine design: Helical wheel homology predicts antibody cross-reactivity among streptococcal M protein–derived peptides

Journal of Biological Chemistry ◽

10.1074/jbc.ra119.011258 ◽

2020 ◽

Vol 295 (12) ◽

pp. 3826-3836 ◽

Cited By ~ 1

Author(s):

Michelle P. Aranha ◽

Thomas A. Penfound ◽

Jay A. Spencer ◽

Rupesh Agarwal ◽

Jerome Baudry ◽

...

Keyword(s):

Group A Streptococcus ◽

Coiled Coil ◽

Cross Reactivity ◽

M Protein ◽

High Sequence Identity ◽

Sequence Identity ◽

Streptococcal M Protein ◽

Helical Wheel ◽

Group A ◽

Immunological Assays

Group A streptococcus (Strep A) surface M protein, an α-helical coiled-coil dimer, is a vaccine target and a major determinant of streptococcal virulence. The sequence-variable N-terminal region of the M protein defines the M type and also contains epitopes that promote opsonophagocytic killing of streptococci. Recent reports have reported considerable cross-reactivity among different M types, suggesting the prospect of identifying cross-protective epitopes that would constitute a broadly protective multivalent vaccine against Strep A isolates. Here, we have used a combination of immunological assays, structural biology, and cheminformatics to construct a recombinant M protein–based vaccine that included six Strep A M peptides that were predicted to elicit antisera that would cross-react with an additional 15 nonvaccine M types of Strep A. Rabbit antisera against this recombinant vaccine cross-reacted with 10 of the 15 nonvaccine M peptides. Two of the five nonvaccine M peptides that did not cross-react shared high sequence identity (≥50%) with the vaccine peptides, implying that high sequence identity alone was insufficient for cross-reactivity among the M peptides. Additional structural analyses revealed that the sequence identity at corresponding polar helical-wheel heptad sites between vaccine and nonvaccine peptides accurately distinguishes cross-reactive from non–cross-reactive peptides. On the basis of these observations, we developed a scoring algorithm based on the sequence identity at polar heptad sites. When applied to all epidemiologically important M types, this algorithm should enable the selection of a minimal number of M peptide–based vaccine candidates that elicit broadly protective immunity against Strep A.

Download Full-text

Characterization of Shiga Toxin 2a Encoding Bacteriophages Isolated From High-Virulent O145:H25 Shiga Toxin-Producing Escherichia coli

Frontiers in Microbiology ◽

10.3389/fmicb.2021.728116 ◽

2021 ◽

Vol 12 ◽

Author(s):

Silje N. Ramstad ◽

Yngvild Wasteson ◽

Bjørn-Arne Lindstedt ◽

Arne M. Taxt ◽

Jørgen V. Bjørnholt ◽

...

Keyword(s):

Escherichia Coli ◽

Shiga Toxin ◽

Integration Site ◽

Severe Disease ◽

High Sequence Identity ◽

Shiga Toxins ◽

Sequence Identity ◽

Diarrhea Case ◽

The Usa ◽

Uremic Syndrome

Shiga toxin-producing Escherichia coli (STEC) may cause severe disease mainly due to the ability to produce Shiga toxins (Stx) encoded on bacteriophages. In Norway, more than 30% of the reported cases with STEC O145:H25 develop hemolytic uremic syndrome (HUS), and most cases, with known travel history, acquired the infection domestically. To describe phage characteristics associated with high virulence, we extracted the Stx2a phage sequences from eight clinical Norwegian O145:H25 STEC to conduct in-depth molecular characterization using long and short read sequencing. The Stx2a phages were annotated, characterized, and compared with previously published Stx2a phages isolated from STEC of different serotypes. The Norwegian O145:H25 Stx2a phages showed high sequence identity (>99%) with 100% coverage. The Stx2a phages were located at the integration site yciD, were approximately 45 kbp long, and harbored several virulence-associated genes, in addition to stx2a, such as nanS and nleC. We observed high sequence identity (>98%) and coverage (≥94%) between Norwegian O145:H25 Stx2a phages and publicly available Stx2a phages from O145:H25 and O145:H28 STEC, isolated from HUS cases in the USA and a hemorrhagic diarrhea case from Japan, respectively. However, low similarity was seen when comparing the Norwegian O145:H25 Stx2a phage to Stx2a phages from STEC of other serotypes. In all the Norwegian O145:H25 STEC, we identified a second phage or remnants of a phage (a shadow phage, 61 kbp) inserted at the same integration site as the Stx2a phage. The shadow phage shared similarity with the Stx2a phage, but lacked stx2a and harbored effector genes not present in the Stx2a phage. We identified a conserved Stx2a phage among the Norwegian O145:H25 STEC that shared integration site with a shadow phage in all isolates. Both phage and shadow phage harbored several virulence-associated genes that may contribute to the increased pathogenicity of O145:H25 STEC.

Download Full-text

Yeast Plasma Membrane Fungal Oligopeptide Transporters Display Distinct Substrate Preferences despite Their High Sequence Identity

Journal of Fungi ◽

10.3390/jof7110963 ◽

2021 ◽

Vol 7 (11) ◽

pp. 963

Author(s):

Carmen Becerra-Rodríguez ◽

Géraldine Taghouti ◽

Perrine Portier ◽

Sylvie Dequin ◽

Margarida Casal ◽

...

Keyword(s):

Gene Expression ◽

Plasma Membrane ◽

Family Members ◽

Sequence Divergence ◽

High Sequence Identity ◽

Yeast Plasma Membrane ◽

Sequence Identity ◽

Substrate Preferences ◽

Wine Strain ◽

Phenotype Microarrays

Fungal Oligopeptide Transporters (Fot) Fot1, Fot2 and Fot3 have been found in Saccharomyces cerevisiae wine strains, but not in strains from other environments. In the S. cerevisiae wine strain EC1118, Fot1 and Fot2 are responsible for a broader range of oligopeptide utilization in comparison with strains not containing any Fot. This leads to better fermentation efficiency and an increased production of desirable organoleptic compounds in wine. Despite the benefits associated with Fot activity in S. cerevisiae within the wine environment, little is known about this family of transporters in yeast. The presence of Fot1, Fot2 and Fot3 in S. cerevisiae wine strains is due to horizontal gene transfer from the yeast Torulaspora microellipsoides, which harbors Fot2Tm, FotX and FotY proteins. Sequence analyses revealed that Fot family members have a high sequence identity in these yeast species. In this work, we aimed to further characterize the different Fot family members in terms of subcellular localization, gene expression in enological fermentation and substrate specificity. Using CRISPR/Cas9, we constructed S. cerevisiae wine strains containing each different Fot as the sole oligopeptide transporter to analyze their oligopeptide preferences by phenotype microarrays. The results of oligopeptide consumption show that Fot counterparts have different di-/tripeptide specificities, suggesting that punctual sequence divergence between FOT genes can be crucial for substrate recognition, binding and transport activity. FOT gene expression levels in different S. cerevisiae wine strains during enological fermentation, together with predicted binding motifs for transcriptional regulators in nitrogen metabolism, indicate that these transporters may be under the control of the Nitrogen Catabolite Repression (NCR) system. Finally, we demonstrated that Fot1 is located in the yeast plasma membrane. This work contributes to a better understanding of this family of oligopeptide transporters, which have demonstrated a key role in the utilization of oligopeptides by S. cerevisiae in enological fermentation.

Download Full-text

The impact of super-spreaders in COVID-19: mapping genome variation worldwide

10.1101/2020.05.19.097410 ◽

2020 ◽

Cited By ~ 4

Author(s):

Alberto Gómez-Carballa ◽

Xabier Bello ◽

Jacobo Pardo-Seco ◽

Federico Martinón-Torres ◽

Antonio Salas

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Founder Effect ◽

Human Pathogen ◽

High Sequence Identity ◽

Asian Origin ◽

Sequence Identity ◽

Public Repositories ◽

The Impact ◽

Bat Coronavirus ◽

Virus Strains

AbstractThe human pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the major pandemic of the 21st century. We analyzed >4,700 SARS-CoV-2 genomes and associated meta-data retrieved from public repositories. SARS-CoV-2 sequences have a high sequence identity (>99.9%), which drops to >96% when compared to bat coronavirus. We built a mutation-annotated reference SARS-CoV-2 phylogeny with two main macro-haplogroups, A and B, both of Asian origin, and >160 sub-branches representing virus strains of variable geographical origins worldwide, revealing a uniform mutation occurrence along branches that could complicate the design of future vaccines. The root of SARS-CoV-2 genomes locates at the Chinese haplogroup B1, with a TMRCA dating to 12 November 2019 - thus matching epidemiological records. Sub-haplogroup A2a originates in China and represents the major non-Asian outbreak. Multiple founder effect episodes, most likely associated with super-spreader hosts, explain COVID-19 pandemic to a large extent.

Download Full-text

Antibodies against immunogenic epitopes with high sequence identity to SARS-CoV-2 in patients with autoimmune dermatomyositis

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-217522 ◽

2020 ◽

Vol 79 (10) ◽

pp. 1383-1386 ◽

Cited By ~ 13

Author(s):

Spyridon Megremis ◽

Thomas D J Walker ◽

Xiaotong He ◽

William E R Ollier ◽

Hector Chinoy ◽

...

Keyword(s):

High Sequence Identity ◽

Sequence Identity

Download Full-text

Structure-based Approaches Targeting Parasite Cysteine Proteases

Current Medicinal Chemistry ◽

10.2174/0929867324666170810165302 ◽

2019 ◽

Vol 26 (23) ◽

pp. 4435-4453 ◽

Cited By ~ 5

Author(s):

Rafael Pinto Vieira ◽

Viviane Corrêa Santos ◽

Rafaela Salgado Ferreira

Keyword(s):

Neurodegenerative Disease ◽

Hydrolytic Enzymes ◽

Cysteine Proteases ◽

Structural Features ◽

High Sequence Identity ◽

Sequence Identity ◽

Pathological Conditions ◽

Therapeutic Tools ◽

Synthetic Approaches ◽

Specific Inhibitors

Cysteine proteases are essential hydrolytic enzymes present in the majority of organisms, including viruses and unicellular parasites. Despite the high sequence identity displayed among these proteins, specific structural features across different species grant distinct functions to these biomolecules, frequently related to pathological conditions. Consequently, their relevance as promising targets for potential specific inhibitors has been highlighted and occasionally validated in recent decades. In this review, we discuss the recent outcomes of structure-based campaigns aiming the discovery of new inhibitor prototypes against cruzain and falcipain, as alternative therapeutic tools for Chagas disease and malaria treatments, respectively. Computational and synthetic approaches have been combined on hit optimization strategies and are also discussed herein. These rationales are extended to additional tropical infectious and neglected pathologies, such as schistosomiasis, leishmaniasis and babesiosis, and also to Alzheimer’s Disease, a widespread neurodegenerative disease poorly managed by currently available drugs and recently linked to particular physiopathological roles of human cysteine proteases.

Download Full-text

Faculty Opinions recommendation of NMR structures of two designed proteins with high sequence identity but different fold and function.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1124240.602251 ◽

2009 ◽

Author(s):

Nick Grishin

Keyword(s):

High Sequence Identity ◽

Sequence Identity ◽

Nmr Structures ◽

Designed Proteins ◽

And Function

Download Full-text

In silico Prediction and Designing of Potential siRNAs to be Used as Antivirals Against SARS-CoV-2

Current Pharmaceutical Design ◽

10.2174/1381612827999210111194101 ◽

2021 ◽

Vol 27 ◽

Author(s):

Sayed Sartaj Sohrab ◽

Sherif Aly El-Kafrawy ◽

Aymn T. Abbas ◽

Leena H. Bajrai ◽

Esam Ibraheem Azhar

Keyword(s):

Genetic Diversity ◽

Sequence Analysis ◽

Phylogenetic Relationships ◽

In Silico ◽

Full Genome ◽

In Silico Prediction ◽

High Sequence Identity ◽

Minor Parent ◽

Sequence Identity ◽

The City

Background:: The unusual pneumonia outbreak that originated in the city of Wuhan, China in December 2019 was found to be caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or COVID-19. Methods:: In this work, we have performed an in silico design and prediction of potential siRNAs based on genetic diversity and recombination patterns, targeting various genes of SARS-CoV-2 for antiviral therapeutics. We performed extensive sequence analysis to analyze the genetic diversity and phylogenetic relationships, and to identify the possible source of virus reservoirs and recombination patterns, and the evolution of the virus as well as we designed the siRNAs which can be used as antivirals against SARS-CoV-2. Results:: The sequence analysis and phylogenetic relationships indicated high sequence identity and closed clusters with many types of coronavirus. In our analysis, the full-genome of SARS-CoV-2 showed the highest sequence (nucleotide) identity with SARS-bat-ZC45 (87.7%). The overall sequence identity ranged from 74.3% to 87.7% with selected SARS viruses. The recombination analysis indicated the bat SARS virus is a potential recombinant and serves as a major and minor parent. We have predicted 442 siRNAs and finally selected only 19 functional, and potential siRNAs. Conclusions:: The siRNAs were predicted and selected based on their greater potency and specificity. The predicted siRNAs need to be validated experimentally for their effective binding and antiviral activity.

Download Full-text