In silico analyses of CD14 molecule reveals significant evolutionary diversity potentially associated with speciation and variable immune response in mammals

Species Response ◽

Gene Coding ◽

Protein Interactome ◽

Mutational Hotspots ◽

Cluster differentiation gene (CD14) is a family of monocyte differentiating genes that works in conjunction with lipopolysaccharide binding protein (LBP), forming a complex with TLR4 or LY96 to mediate innate immune response to pathogens. In this paper, we used different computational methods to elucidate the evolution of CD14 gene coding region in 14 mammalian species. Our analyses identified leucine rich repeats (LRRs) as the only significant domain across the CD14 protein of the 14 species, presenting with frequencies ranging from 1-4. Importantly, we found signal peptides located at mutational hotspots demonstrating this gene is conserved across these species. Out of the 10 selected variants analyzed in this study, only 6 were predicted to possess significant deleterious effect. Our predicted protein interactome showed a significant varying protein-protein interaction with CD14 protein across the species. This may be important for drug target and therapeutic manipulation for the treatment of many diseases. We conclude that these results contribute to our understanding of the CD14 molecular evolution, which underlays varying species response to complex disease traits.

In silico analyses of CD14 molecule reveal significant evolutionary diversity, potentially associated with speciation and variable immune response in mammals

PeerJ ◽

10.7717/peerj.7325 ◽

2019 ◽

Vol 7 ◽

pp. e7325 ◽

Cited By ~ 3

Author(s):

Olanrewaju B. Morenikeji ◽

Bolaji N. Thomas

Keyword(s):

Immune Response ◽

Complex Disease ◽

Mammalian Species ◽

Coding Region ◽

Species Response ◽

Gene Coding ◽

Protein Interactome ◽

Mutational Hotspots ◽

The cluster differentiation gene (CD14) is a family of monocyte differentiating genes that works in conjunction with lipopolysaccharide binding protein, forming a complex with TLR4 or LY96 to mediate innate immune response to pathogens. In this paper, we used different computational methods to elucidate the evolution of CD14 gene coding region in 14 mammalian species. Our analyses identified leucine-rich repeats as the only significant domain across the CD14 protein of the 14 species, presenting with frequencies ranging from one to four. Importantly, we found signal peptides located at mutational hotspots demonstrating that this gene is conserved across these species. Out of the 10 selected variants analyzed in this study, only six were predicted to possess significant deleterious effect. Our predicted protein interactome showed a significant varying protein–protein interaction with CD14 protein across the species. This may be important for drug target and therapeutic manipulation for the treatment of many diseases. We conclude that these results contribute to our understanding of the CD14 molecular evolution, which underlays varying species response to complex disease traits.

In silico analyses of CD14 molecule reveals significant evolutionary diversity potentially associated with speciation and variable immune response in mammals

10.7287/peerj.preprints.27668v1 ◽

2019 ◽

Author(s):

Olanrewaju B Morenikeji ◽

Bolaji N Thomas

Keyword(s):

Immune Response ◽

Complex Disease ◽

Mammalian Species ◽

Coding Region ◽

Species Response ◽

Gene Coding ◽

Protein Interactome ◽

Mutational Hotspots ◽

Cluster differentiation gene (CD14) is a family of monocyte differentiating genes that works in conjunction with lipopolysaccharide binding protein (LBP), forming a complex with TLR4 or LY96 to mediate innate immune response to pathogens. In this report, we used different computational methods to elucidate the evolution of CD14 gene coding region in 14 mammalian species. Our analyses identified leucine rich repeats (LRRs) as the only significant domain across the CD14 protein of the 14 species with varying frequencies. Importantly, we found signal peptides located at mutational hotspots demonstrating this gene has ancient conservation across these species. Out of the 10 selected variants analyzed in this study, only 6 were predicted to possess significant deleterious effect. Our predicted protein interactome showed a significant varying protein-protein interaction with CD14 protein across the species. This is important for drug target and therapeutic manipulation for the treatment of many diseases. We conclude that these results contribute to our understanding of the CD14 molecular evolution, which underlays varying species response to complex disease traits.

In silico analyses of CD14 molecule reveals significant evolutionary diversity potentially associated with speciation and variable immune response in mammals

10.7287/peerj.preprints.27668v2 ◽

2019 ◽

Author(s):

Olanrewaju B Morenikeji ◽

Bolaji N Thomas

Keyword(s):

Immune Response ◽

Complex Disease ◽

Mammalian Species ◽

Coding Region ◽

Species Response ◽

Gene Coding ◽

Protein Interactome ◽

Mutational Hotspots ◽

In vivo interactome profiling by enzyme‐catalyzed proximity labeling

Cell & Bioscience ◽

10.1186/s13578-021-00542-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yangfan Xu ◽

Xianqun Fan ◽

Yang Hu

Keyword(s):

State Of The Art ◽

Catalytic Efficiency ◽

Biological Processes ◽

Current State ◽

Protein Interactome ◽

Potential Applications ◽

Protein Protein Interaction Networks ◽

Temporal And Spatial

AbstractEnzyme-catalyzed proximity labeling (PL) combined with mass spectrometry (MS) has emerged as a revolutionary approach to reveal the protein-protein interaction networks, dissect complex biological processes, and characterize the subcellular proteome in a more physiological setting than before. The enzymatic tags are being upgraded to improve temporal and spatial resolution and obtain faster catalytic dynamics and higher catalytic efficiency. In vivo application of PL integrated with other state of the art techniques has recently been adapted in live animals and plants, allowing questions to be addressed that were previously inaccessible. It is timely to summarize the current state of PL-dependent interactome studies and their potential applications. We will focus on in vivo uses of newer versions of PL and highlight critical considerations for successful in vivo PL experiments that will provide novel insights into the protein interactome in the context of human diseases.

A case of rare allele T 126, 30,32 base pairs in a schizophrenic patient: A study case

European Psychiatry ◽

10.1016/j.eurpsy.2016.01.2173 ◽

2016 ◽

Vol 33 (S1) ◽

pp. S585-S586

Author(s):

A.I. Sabau ◽

P. Cristina ◽

B. Valerica ◽

P. Delia Marina

Keyword(s):

Schizophrenic Patient ◽

Complex Disease ◽

Susceptibility Gene ◽

Rflp Analysis ◽

Rare Allele ◽

Base Pairs ◽

Gene Coding ◽

Icd 10 ◽

Schizophrenic Patients ◽

Competing Interest

IntroductionSchizophrenia is a severe and complex disease clinically characterized by disturbed thought processes, delusions, hallucinations and reduced social skills. Gene coding for neregulin 1 (NRG 1) located in 8 p21chromosomeand single nucleotide polymorphism (SNPs) have been identified strongly supporting NRG1 gene as a susceptibility gene for schizophrenia.ObjectiveThe present preliminary study, determines the relationship between polymorphism nucleotide sites (SNPs2) of NRG1 gene and schizophrenia.AimsIdentifying rare allele T of neregulin 1 genein schizophrenic patients.MethodWe analyzed the polymorphism (SNPs2) of NRG1 gene in 20 patients recruited from Psychiatry Department of Emergency Clinical Hospital of Arad diagnosed with schizophrenia according to DSM-5-TM and ICD-10 criteria and 10 healthy controls. From all subjects, we obtained 2 mL of peripheral blood samples. Genomic DNA was extracted using the phenol-chloroform method. Genotyping was performed byPCR-based RFLP analysis for all subjects. The obtained PCR product mixture was completely digested with restriction enzyme, separated on SNP1 and SNP2 agarose gel. We present the case of a 31 years old, male, schizophrenic patient with the SNPs2 polymorphism and rare allele T 126.ResultsIn both groups, common allele G 127 and 60 base pairs was identified but only 2 schizophrenic patients presented rare allele T 126 and 30,32 base pairs.ConclusionsThe polymorphism SNPs2 of NRG1 gene with rare allele T 126 and 30,32 base pairs, may play a role in predisposing an individual to schizophrenia. Further and extended replicating studies with multiple sequencing of NRG1 gene are necessary.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Retinoschisis and Norrie Disease: A missing link

10.21203/rs.3.rs-322315/v1 ◽

2021 ◽

Author(s):

Rahini Rajendran ◽

Sudha Dhandayuthapani ◽

Subbulakshmi Chidambaram ◽

Hemavathy Nagarajan ◽

Umashankar Vetrivel ◽

...

Keyword(s):

Mass Spectrometry ◽

Functional Relationship ◽

Direct Interaction ◽

Specific Protein ◽

Knock Out ◽

Norrie Disease ◽

Protein Interactome ◽

Molecular Relationships

Abstract Objective: Retinoschisis and Norrie disease are X-linked recessive retinal disorders caused by mutations in RS1 and NDP genes respectively. Both are likely to be monogenic and no locus heterogeneity has been reported. However, there are reports showing overlapping features of Norrie disease and retinoschisis in a NDP knock-out mouse model and also the involvement of both the genes in retinoschisis patients. Yet, the exact molecular relationships between the two disorders have still not been understood. The study investigated the association between retinoschisin (RS1) and norrin (NDP) using in vitro and in silico approaches. Specific protein-protein interaction between RS1 and NDP was analyzed in human retina by co-immunoprecipitation assay and MALDI-TOF mass spectrometry. STRING database was used to explore the functional relationship. Result: Co-immunoprecipitation demonstrated lack of a direct interaction between RS1 and NDP and was further substantiated by mass spectrometry. However, STRING revealed a potential indirect functional association between the two proteins. Progressively, our analyses indicate that FZD4 protein interactome via PLIN2 as well as the MAP kinase signaling pathway to be a likely link bridging the functional relationship between retinoschisis and Norrie disease.

Conserved charged residues in the leucine-rich repeat domain of the Ran GTPase activating protein are required for Ran binding and GTPase activation

Biochemical Journal ◽

10.1042/bj3430653 ◽

1999 ◽

Vol 343 (3) ◽

pp. 653-662 ◽

Cited By ~ 12

Author(s):

Jörg HABERLAND ◽

Volker GERKE

Keyword(s):

Nucleocytoplasmic Transport ◽

Small Gtpases ◽

Structural Basis ◽

Ran Gtpase ◽

Charged Residues ◽

Gtpase Activation ◽

Gtpase Cycle ◽

Leucine Rich Repeats ◽

Lrr Domain

GTPase activating proteins (GAPs) for Ran, a Ras-related GTPase participating in nucleocytoplasmic transport, have been identified in different species ranging from yeast to man. All RanGAPs are characterized by a conserved domain consisting of eight leucine-rich repeats (LRRs) interrupted at two positions by so-called separating regions, the latter being unique for RanGAPs within the family of LRR proteins. The cytosolic RanGAP activity is essential for the Ran GTPase cycle which in turn provides directionality in nucleocytoplasmic transport, but the structural basis for the interaction between Ran and its GAP has not been elucidated. In order to gain a better understanding of this interaction we generated a number of mutant RanGAPs carrying amino acid substitutions in the LRR domain and analysed their complex formation with Ran as well as their ability to stimulate the intrinsic GTPase activity of the G protein. We show that conserved charged residues present in the separating regions of the LRR domain are indispensable for efficient Ran binding and GAP activity. These separating regions contain three conserved arginines which could possibly serve as catalytic residues similar to the arginine fingers identified in GAPs for other small GTPases. However, mutations in two of these arginines do not affect the GAP activity and replacement of the third conserved arginine (Arg91 in human RanGAP) severely interferes not only with GAP activity but also with Ran binding. This indicates that RanGAP-stimulated GTP hydrolysis on Ran does not involve a catalytic arginine residue but requires certain charged residues of the LRR domain of the GAP for mediating the protein-protein interaction.

Exploring the Protein Interactome Related to Hepatitis C Virus

NUST Journal of Natural Sciences ◽

10.53992/njns.v3i1.15 ◽

2021 ◽

Vol 3 (1) ◽

pp. 13-18

Author(s):

Shifa Ashraf ◽

Marriam Bakhtiar

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Liver Diseases ◽

Complex Disease ◽

Network Science ◽

Topological Analysis ◽

System Level ◽

Molecular Connectivity ◽

Regulatory Pathways ◽

Protein Interactome

Hepatitis C virus (HCV) stands as a health problem experienced across the globe leading to chronic or acute liver diseases such as cirrhosis, hepatocellular carcinoma and various others. It is a complex disease with extensive genetic heterogeneity with little known about the interactions of complex intra- and intercellular processes. The evolving tools in the application of network science to identify diseases have paved a way for the study of complex diseases at system level. This study focuses on identifying the significant proteins and the biological regulatory pathways involved in Hepatitis C virus and performing topological analysis of the PPIs derived by the proteins encoded by the susceptible genes in order to look for the molecular connectivity between these pathways.icant proteins and the biological regulatory pathways involved in Hepatitis C virus and performing topological analysis of the PPIs derived by the proteins encoded by the susceptible genes in order to look for the molecular connectivity between these pathways.

Complex method of the prognosis of tick-born neuroinfections

Bulletin of Siberian Medicine ◽

10.20538/1682-0363-2008-5-2-420-423 ◽

2008 ◽

Vol 7 (5-2) ◽

pp. 420-423

Author(s):

A. V. Subbotin ◽

V. A. Semyonov ◽

I. Yu. Torshin ◽

O. A. Gromova ◽

Ye. V. Fyodorova ◽

...

Keyword(s):

Immune Response ◽

Risk Factor ◽

Catalytic Activity ◽

Rna Viruses ◽

Clinical Manifestations ◽

Important Risk Factor ◽

Biochemical Data ◽

Complex Method ◽

Gene Coding ◽

Tick Borne Encephalitis

Here, we propose a method of forecasting the development of the heavy forms of the tick-borne encephalitis using diagnostic tables. The method is based on evaluation of the patients with syndrome of endogenous intoxication using immunological and biochemical data along with evaluation of the clinical manifestations. We also propose an advanced form of the method that includes data based on the genotype of OAS1 — the gene, coding oligonucleotidesynthetase needed for immune response to RNA viruses. OAS1 genotype is an important risk factor since the differences in catalytic activity of OAS1 isoenzymes result in different susceptibility to the virus of the tick-borne encephalitis.

Colletotrichum Gloeosporioides Species Complex

Identification of the Colletotrichum species associated with mango diseases and a universal LAMP detection method for C. gloeosporioides species complex

Plant & Fungal Research ◽

10.30546/2664-5297.2021.1.49. ◽

2021 ◽

pp. 49-60

Author(s):

Yukako Hattori ◽

Chiharu Nakashima ◽

Shunsuke Kitabata ◽

Kosuke Naito ◽

Ayaka Hieno ◽

...

Keyword(s):

Species Complex ◽

Plant Disease ◽

Plant Pathogens ◽

Colletotrichum Gloeosporioides ◽

Detection Method ◽

Coding Region ◽

Gene Coding ◽

Detectable Range ◽

Amplification Assay ◽

Abstract: The Colletotrichum gloeosporioides species complex contains plant pathogens linked to Anthracnose diseases afflicting various crops. In this study, we designed a loop-mediated isothermal amplification assay (LAMP) primer set based on calmodulin gene coding region sequences from taxonomically authorized isolates of species from this complex to rapidly detect the presence of fungi associated with Anthracnose diseases. This test can be employed at any point between cultivation and sale. Moreover, we examined the specificity and detectable range of this primer set using isolates selected from species of the genus Colletotrichum. This test was able to specifically detect members of the C. gloeosporioides species complex, including C. gloeosporioides, C. aotearoa, C. fructicola, C. horii, C. kahawae, C. musae, C. siamense, C. theobromicola, and C. tropicale. Key Words: Anthracnose, diagnosis, phylogeny, plant disease