Compensatory expression regulation of highly homologous proteins HNRNPA1 and HNRNPA2

Abstract Background The SARS-CoV-2 virus, the causative agent of COVID-19, consists of an assembly of proteins that determine its infectious and immunological behavior, as well as its response to therapeutics. Major structural biology efforts on these proteins have already provided essential insights into the mode of action of the virus, as well as avenues for structure-based drug design. However, not all of the SARS-CoV-2 proteins, or regions thereof, have a well-defined three-dimensional structure, and as such might exhibit ambiguous, dynamic behaviour that is not evident from static structure representations, nor from molecular dynamics simulations using these structures. Main We present a website (https://bio2byte.be/sars2/) that provides protein sequence-based predictions of the backbone and side-chain dynamics and conformational propensities of these proteins, as well as derived early folding, disorder, β-sheet aggregation, protein-protein interaction and epitope propensities. These predictions attempt to capture the inherent biophysical propensities encoded in the sequence, rather than context-dependent behaviour such as the final folded state. In addition, we provide the biophysical variation that is observed in homologous proteins, which gives an indication of the limits of their functionally relevant biophysical behaviour. Conclusion The https://bio2byte.be/sars2/ website provides a range of protein sequence-based predictions for 27 SARS-CoV-2 proteins, enabling researchers to form hypotheses about their possible functional modes of action.

Download Full-text

Signatures of conserved and unique molecular features in Afrotheria

Scientific Reports ◽

10.1038/s41598-020-79559-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Arangasamy Yazhini ◽

Narayanaswamy Srinivasan ◽

Sankaran Sandhya

Keyword(s):

Ribosomal Proteins ◽

Individual Species ◽

Functional Domain ◽

Nucleic Acid Binding ◽

Uncharacterized Protein ◽

Homologous Proteins ◽

Functional Roles ◽

Molecular Features ◽

Specific Proteins ◽

Species Specific

AbstractAfrotheria is a clade of African-origin species with striking dissimilarities in appearance and habitat. In this study, we compared whole proteome sequences of six Afrotherian species to obtain a broad viewpoint of their underlying molecular make-up, to recognize potentially unique proteomic signatures. We find that 62% of the proteomes studied here, predominantly involved in metabolism, are orthologous, while the number of homologous proteins between individual species is as high as 99.5%. Further, we find that among Afrotheria, L. africana has several orphan proteins with 112 proteins showing < 30% sequence identity with their homologues. Rigorous sequence searches and complementary approaches were employed to annotate 156 uncharacterized protein sequences and 28 species-specific proteins. For 122 proteins we predicted potential functional roles, 43 of which we associated with protein- and nucleic-acid binding roles. Further, we analysed domain content and variations in their combinations within Afrotheria and identified 141 unique functional domain architectures, highlighting proteins with potential for specialized functions. Finally, we discuss the potential relevance of highly represented protein families such as MAGE-B2, olfactory receptor and ribosomal proteins in L. africana and E. edwardii, respectively. Taken together, our study reports the first comparative study of the Afrotherian proteomes and highlights salient molecular features.

Download Full-text

Legionella pneumophila DotU and IcmF Are Required for Stability of the Dot/Icm Complex

Infection and Immunity ◽

10.1128/iai.72.10.5983-5992.2004 ◽

2004 ◽

Vol 72 (10) ◽

pp. 5983-5992 ◽

Cited By ~ 56

Author(s):

Jessica A. Sexton ◽

Jennifer L. Miller ◽

Aki Yoneda ◽

Thomas E. Kehl-Fie ◽

Joseph P. Vogel

Keyword(s):

Cell Surface ◽

Legionella Pneumophila ◽

Bacterial Species ◽

Wide Distribution ◽

Host Cells ◽

Growth Defect ◽

Intracellular Growth ◽

Homologous Proteins ◽

Type Iv ◽

Cell Surface Structure

ABSTRACT Legionella pneumophila utilizes a type IV secretion system (T4SS) encoded by 26 dot/icm genes to replicate inside host cells and cause disease. In contrast to all other L. pneumophila dot/icm genes, dotU and icmF have homologs in a wide variety of gram-negative bacteria, none of which possess a T4SS. Instead, dotU and icmF orthologs are linked to a locus encoding a conserved cluster of proteins designated IcmF-associated homologous proteins, which has been proposed to constitute a novel cell surface structure. We show here that dotU is partially required for L. pneumophila intracellular growth, similar to the known requirement for icmF. In addition, we show that dotU and icmF are necessary for optimal plasmid transfer and sodium sensitivity, two additional phenotypes associated with a functional Dot/Icm complex. We found that these effects are due to the destabilization of the T4SS at the transition into the stationary phase, the point at which L. pneumophila becomes virulent. Specifically, three Dot proteins (DotH, DotG, and DotF) exhibit decreased stability in a ΔdotU ΔicmF strain. Furthermore, overexpression of just one of these proteins, DotH, is sufficient to suppress the intracellular growth defect of the ΔdotU ΔicmF mutant. This suggests a model where the DotU and IcmF proteins serve to prevent DotH degradation and therefore function to stabilize the L. pneumophila T4SS. Due to their wide distribution among bacterial species and their genetic linkage to known or predicted cell surface structures, we propose that this function in complex stabilization may be broadly conserved.

Download Full-text

Network-based analysis of virulence factors for uncovering Aeromonas veronii pathogenesis

BMC Microbiology ◽

10.1186/s12866-021-02261-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Hong Li ◽

Xiang Ma ◽

Yanqiong Tang ◽

Dan Wang ◽

Ziding Zhang ◽

...

Keyword(s):

Virulence Factors ◽

Bacterial Pathogen ◽

Signal Transduction Pathway ◽

Immune Defense ◽

Ppi Network ◽

Host Proteins ◽

Homologous Proteins ◽

Aeromonas Veronii ◽

Regulatory Systems ◽

Network Modules

Abstract Background Aeromonas veronii is a bacterial pathogen in aquaculture, which produces virulence factors to enable it colonize and evade host immune defense. Given that experimental verification of virulence factors is time-consuming and laborious, few virulence factors have been characterized. Moreover, most studies have only focused on single virulence factors, resulting in biased interpretation of the pathogenesis of A. veronii. Results In this study, a PPI network at genome-wide scale for A. veronii was first constructed followed by prediction and mapping of virulence factors on the network. When topological characteristics were analyzed, the virulence factors had higher degree and betweenness centrality than other proteins in the network. In particular, the virulence factors tended to interact with each other and were enriched in two network modules. One of the modules mainly consisted of histidine kinases, response regulators, diguanylate cyclases and phosphodiesterases, which play important roles in two-component regulatory systems and the synthesis and degradation of cyclic-diGMP. Construction of the interspecies PPI network between A. veronii and its host Oreochromis niloticus revealed that the virulence factors interacted with homologous proteins in the host. Finally, the structures and interacting sites of the virulence factors during interaction with host proteins were predicted. Conclusions The findings here indicate that the virulence factors probably regulate the virulence of A. veronii by involving in signal transduction pathway and manipulate host biological processes by mimicking and binding competitively to host proteins. Our results give more insight into the pathogenesis of A. veronii and provides important information for designing targeted antibacterial drugs.

Download Full-text