scholarly journals Intrinsic disorder in protein domains contributes to both organism complexity and clade-specific functions

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chao Gao ◽  
Chong Ma ◽  
Huqiang Wang ◽  
Haolin Zhong ◽  
Jiayin Zang ◽  
...  
Keyword(s):  
Biological Significance ◽  
Protein Domains ◽  
Functional Requirements ◽  
Post Translational Modification ◽  
Intrinsically Disordered ◽  
Genome Wide ◽  
Complex Functions ◽  
Disorder Degree ◽  
Functional Features ◽  
And Function

AbstractInterestingly, some protein domains are intrinsically disordered (abbreviated as IDD), and the disorder degree of same domains may differ in different contexts. However, the evolutionary causes and biological significance of these phenomena are unclear. Here, we address these issues by genome-wide analyses of the evolutionary and functional features of IDDs in 1,870 species across the three superkingdoms. As the result, there is a significant positive correlation between the proportion of IDDs and organism complexity with some interesting exceptions. These phenomena may be due to the high disorder of clade-specific domains and the different disorder degrees of the domains shared in different clades. The functions of IDDs are clade-specific and the higher proportion of post-translational modification sites may contribute to their complex functions. Compared with metazoans, fungi have more IDDs with a consecutive disorder region but a low disorder ratio, which reflects their different functional requirements. As for disorder variation, it’s greater for domains among different proteins than those within the same proteins. Some clade-specific ‘no-variation’ or ‘high-variation’ domains are involved in clade-specific functions. In sum, intrinsic domain disorder is related to both the organism complexity and clade-specific functions. These results deepen the understanding of the evolution and function of IDDs.

scholarly journals The Distinct Properties of the Consecutive Disordered Regions Inside or Outside Protein Domains and Their Functional Significance

2021 ◽  
Vol 22 (19) ◽  
pp. 10677
Author(s):  
Huqiang Wang ◽  
Haolin Zhong ◽  
Chao Gao ◽  
Jiayin Zang ◽  
Dong Yang
Keyword(s):  
Intrinsically Disordered Proteins ◽  
Protein Domains ◽  
Comprehensive Analysis ◽  
Disordered Proteins ◽  
Functional Constraints ◽  
Biological Functions ◽  
Post Translational Modification ◽  
Intrinsically Disordered ◽  
And Function ◽  
Disordered Regions

The consecutive disordered regions (CDRs) are the basis for the formation of intrinsically disordered proteins, which contribute to various biological functions and increasing organism complexity. Previous studies have revealed that CDRs may be present inside or outside protein domains, but a comprehensive analysis of the property differences between these two types of CDRs and the proteins containing them is lacking. In this study, we investigated this issue from three viewpoints. Firstly, we found that in-domain CDRs are more hydrophilic and stable but have less stickiness and fewer post-translational modification sites compared with out-domain CDRs. Secondly, at the protein level, we found that proteins with only in-domain CDRs originated late, evolved rapidly, and had weak functional constraints, compared with the other two types of CDR-containing proteins. Proteins with only in-domain CDRs tend to be expressed spatiotemporal specifically, but they tend to have higher abundance and are more stable. Thirdly, we screened the CDR-containing protein domains that have a strong correlation with organism complexity. The CDR-containing domains tend to be evolutionarily young, or they changed from a domain without CDR to a CDR-containing domain during evolution. These results provide valuable new insights about the evolution and function of CDRs and protein domains.

scholarly journals 3D Structure and Function of Glycosyltransferases Involved in N-glycan Maturation

2020 ◽  
Vol 21 (2) ◽  
pp. 437 ◽  
Author(s):  
Masamichi Nagae ◽  
Yoshiki Yamaguchi ◽  
Naoyuki Taniguchi ◽  
Yasuhiko Kizuka
Keyword(s):  
Reaction Mechanisms ◽  
Recent Progress ◽  
Protein Transport ◽  
3D Structure ◽  
Biological Significance ◽  
Structure And Function ◽  
Glycan Structure ◽  
Post Translational Modification ◽  
Biochemical Studies ◽  
And Function

Glycosylation is the most ubiquitous post-translational modification in eukaryotes. N-glycan is attached to nascent glycoproteins and is processed and matured by various glycosidases and glycosyltransferases during protein transport. Genetic and biochemical studies have demonstrated that alternations of the N-glycan structure play crucial roles in various physiological and pathological events including progression of cancer, diabetes, and Alzheimer’s disease. In particular, the formation of N-glycan branches regulates the functions of target glycoprotein, which are catalyzed by specific N-acetylglucosaminyltransferases (GnTs) such as GnT-III, GnT-IVs, GnT-V, and GnT-IX, and a fucosyltransferase, FUT8s. Although the 3D structures of all enzymes have not been solved to date, recent progress in structural analysis of these glycosyltransferases has provided insights into substrate recognition and catalytic reaction mechanisms. In this review, we discuss the biological significance and structure-function relationships of these enzymes.

scholarly journals Transcriptomic Analysis of Respiratory Tissue and Cell Line Models to Examine Glycosylation Machinery during SARS-CoV-2 Infection

Viruses ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 82
Author(s):  
Anup Oommen ◽  
Stephen Cunningham ◽  
Lokesh Joshi
Keyword(s):  
Immune Response ◽  
Biological Significance ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Vital Role ◽  
Biomedical Literature ◽  
Transcriptomic Analysis ◽  
Functional Enrichment ◽  
Post Translational Modification ◽  
And Function

Glycosylation, being the most abundant post-translational modification, plays a profound role affecting expression, localization and function of proteins and macromolecules in immune response to infection. Presented are the findings of a transcriptomic analysis performed using high-throughput functional genomics data from public repository to examine the altered transcription of the human glycosylation machinery in response to SARS-CoV-2 stimulus and infection. In addition to the conventional in silico functional enrichment analysis methods we also present results from the manual analysis of biomedical literature databases to bring about the biological significance of glycans and glycan-binding proteins in modulating the host immune response during SARS-CoV-2 infection. Our analysis revealed key immunomodulatory lectins, proteoglycans and glycan epitopes implicated in exerting both negative and positive downstream inflammatory signaling pathways, in addition to its vital role as adhesion receptors for SARS-CoV-2 pathogen. A hypothetical correlation of the differentially expressed human glycogenes with the altered host inflammatory response and the cytokine storm-generated in response to SARS-CoV-2 pathogen is proposed. These markers can provide novel insights into the diverse roles and functioning of glycosylation pathways modulated by SARS-CoV-2, provide avenues of stratification, treatment, and targeted approaches for COVID-19 immunity and other viral infectious agents.

scholarly journals Combinatorial phosphorylation modulates the structure and function of the G protein gamma subunit in yeast

2020 ◽  
Author(s):  
Zahra Nassiri Toosi ◽  
Xinya Su ◽  
Shilpa Choudhury ◽  
Wei Li ◽  
Yui Tik Pang ◽  
...  
Keyword(s):  
G Protein ◽  
Intrinsically Disordered Proteins ◽  
Protein Complexes ◽  
Disordered Proteins ◽  
Post Translational Modification ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Gpcr Activation ◽  
Essential Components ◽  
And Function

AbstractProtein intrinsically disordered regions (IDRs) are often targets of combinatorial post-translational modifications (PTMs) that serve to regulate protein structure and/or function. Emerging evidence suggests that the N-terminal tails of G protein γ subunits – essential components of heterotrimeric G protein complexes – are intrinsically disordered, highly phosphorylated governors of G protein signaling. Here, we demonstrate that the yeast Gγ Ste18 undergoes combinatorial, multi-site phosphorylation within its N-terminal IDR. Phosphorylation at S7 is responsive to GPCR activation and osmotic stress while phosphorylation at S3 is responsive to glucose stress and is a quantitative indicator of intracellular pH. Each site is phosphorylated by a distinct set of kinases and both are also interactive, such that phosphomimicry at one site affects phosphorylation on the other. Lastly, we show that phosphorylation produces subtle yet clear changes in IDR structure and that different combinations of phosphorylation modulate the activation rate and amplitude of the scaffolded MAPK Fus3. These data place Gγ subunits among the growing list of intrinsically disordered proteins that exploit combinatorial post-translational modification to govern signaling pathway output.

Matrix Metalloproteinases in Invertebrates

2020 ◽  
Vol 27 (11) ◽  
pp. 1068-1081
Author(s):  
Xi Liu ◽  
Dongwu Liu ◽  
Yangyang Shen ◽  
Mujie Huang ◽  
Lili Gao ◽  
...  
Keyword(s):  
Matrix Metalloproteinases ◽  
Immune Responses ◽  
Theoretical Basis ◽  
Regulatory Mechanism ◽  
Structure And Function ◽  
Catalytic Domains ◽  
Physiological Processes ◽  
Disease Occurrence ◽  
Complex Functions ◽  
And Function

Matrix Metalloproteinases (MMPs) belong to a family of metal-dependent endopeptidases which contain a series of conserved pro-peptide domains and catalytic domains. MMPs have been widely found in plants, animals, and microorganisms. MMPs are involved in regulating numerous physiological processes, pathological processes, and immune responses. In addition, MMPs play a key role in disease occurrence, including tumors, cardiovascular diseases, and other diseases. Compared with invertebrate MMPs, vertebrate MMPs have diverse subtypes and complex functions. Therefore, it is difficult to study the function of MMPs in vertebrates. However, it is relatively easy to study invertebrate MMPs because there are fewer subtypes of MMPs in invertebrates. In the present review, the structure and function of MMPs in invertebrates were summarized, which will provide a theoretical basis for investigating the regulatory mechanism of MMPs in invertebrates.

Exploring PLAC1 Structure and Underlying Mechanisms to Design a Derivative Vaccine Against Breast Cancer Progression; In-Silico Study

2020 ◽  
Vol 17 (5) ◽  
pp. 379-391
Author(s):  
Farzaneh Afzali ◽  
Parisa Ghahremanifard ◽  
Mohammad Mehdi Ranjbar ◽  
Mahdieh Salimi
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
In Silico ◽  
Tertiary Structure ◽  
Specific Antigen ◽  
Docking Simulation ◽  
Post Translational Modification ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Underlying Mechanisms

Background: The tolerogenic homeostasis in Breast Cancer (BC) can be surpassed by rationally designed immune-encouraging constructs against tumor-specific antigens through immunoinformatics approach. Objective: Availability of high throughput data providing the underlying concept of diseases and awarded computational simulations, lead to screening the potential medications and strategies in less time and cost. Despite the extensive effects of Placenta Specific 1 (PLAC1) in BC progression, immune tolerance, invasion, cell cycle regulation, and being a tumor-specific antigen the fundamental mechanisms and regulatory factors were not fully explored. It is also worth to design an immune response inducing construct to surpass the hurdles of traditional anti-cancer treatments. Methods and Result: The study was initiated by predicting and modelling the PLAC1 secondary and tertiary structures and then engineering the fusion pattern of PLAC1 derived immunodominant predicted CD8+ and B-cell epitopes to form a multi-epitope immunogenic construct. The construct was analyzed considering the physiochemical characterization, safety, antigenicity, post-translational modification, solubility, and intrinsically disordered regions. After modelling its tertiary structure, proteinprotein docking simulation was carried out to ensure the attachment of construct with Toll-Like Receptor 4 (TLR4) as an immune receptor. To guarantee the highest expression of the designed construct in E. coli k12 as an expressional host, the codon optimization and in-silico cloning were performed. The PLAC1 related miRNAs in BC were excavated and validated through TCGA BC miRNA-sequencing and databases; the common pathways then were introduced as other probable mechanisms of PLAC1 activity. Conclusion: Regarding the obtained in-silico results, the designed anti-PLAC1 multi-epitope construct can probably trigger humoral and cellular immune responses and inflammatory cascades, therefore may have the potential of halting BC progression and invasion engaging predicted pathways.

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