scholarly journals The glycine locating at random coil of picornaviruses VP3 enhances viral pathogenicity by targeting p53 to promote apoptosis and autophagy

2019 ◽  
Author(s):  
Ruoqing Mao ◽  
Fan Yang ◽  
Dehui Sun ◽  
Xiaoli Zhou ◽  
Zixiang Zhu ◽  
...  
Keyword(s):  
Enterovirus 71 ◽  
Foot And Mouth Disease ◽  
Underlying Mechanism ◽  
Skin Lesions ◽  
Random Coil ◽  
Autophagy Induction ◽  
Coil Structure ◽  
Mouth Disease Virus ◽  
Random Coil Structure ◽  
Seneca Valley Virus

AbstractPicornaviruses, comprising important and widespread pathogens of humans and animals, have evolved to control apoptosis and autophagy for their replication and spread. However, the underlying mechanism of the association between apoptosis/autophage and viral pathogenicity remains unclear. In the present study, VP3 of picornaviruses was demonstrated to induce apoptosis and autophagy. Foot-and-mouth disease virus (FMDV), which served as a research model here, can strongly induce both apoptosis and autophagy in the skin lesions. By directly interacting with p53, FMDV-VP3 facilitates its phosphorylation and translocation, resulting in Bcl-2 family-mediated apoptosis and LC3-dependent autophagy. The single residue Gly129 of FMDV-VP3 plays a crucial role in apoptosis and autophagy induction and the interaction with p53. Consistently, the comparison of rescued FMDV with mutated Gly129 and parental virus showed that the Gly129 is indispensable for viral replication and pathogenicity. More importantly, the Gly129 locates at a bend region of random coil structure, the mutation of Gly to Ala remarkably shrunk the volume of viral cavity. Coincidentally, the Gly is conserved in the similarly location of other picornaviruses, including poliovirus (PV), enterovirus 71 (EV71), coxsackievirus (CV) and seneca valley virus (SVA). This study demonstrates that picornaviruses induce apoptosis and autophagy to facilitate its pathogenicity and the Gly is functional site, providing novel insights into picornavirus biology.

scholarly journals Foot-and-Mouth Disease Virus 3A Protein Causes Upregulation of Autophagy-Related Protein LRRC25 To Inhibit the G3BP1-Mediated RIG-Like Helicase-Signaling Pathway

2020 ◽  
Vol 94 (8) ◽  
Author(s):  
Wenping Yang ◽  
Dan Li ◽  
Yi Ru ◽  
Juncui Bai ◽  
Jingjing Ren ◽  
...  
Keyword(s):  
Disease Virus ◽  
Enterovirus 71 ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Encephalomyocarditis Virus ◽  
Related Protein ◽  
Antiviral Responses ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Seneca Valley Virus

ABSTRACT Foot-and-mouth disease virus (FMDV) is one of the most notorious pathogens in the global livestock industry. To establish an infection, FMDV needs to counteract host antiviral responses. Several studies have shown how FMDV suppresses the type I interferon (IFN) response; however, whether FMDV modulates the integrated autophagy and innate immunity remains largely unknown. Here, the porcine Ras-GAP SH3-binding protein 1 (G3BP1) was shown to promote the retinoic acid-inducible gene I (RIG-I)-like helicase (RLH) signaling by upregulating the expression of RIG-I and melanoma differentiation-associated gene 5 (MDA5). FMDV nonstructural protein 3A interacted with G3BP1 to inhibit G3BP1 expression and G3BP1-mediated RLH signaling by upregulating the expression of autophagy-related protein LRRC25. In addition, 3A proteins of other picornaviruses, including Seneca Valley virus (SVV) 3A, enterovirus 71 (EV71) 3A, and encephalomyocarditis virus (EMCV) 3A, also showed similar actions. Taking the data together, we elucidated, for the first time, a novel mechanism by which FMDV has evolved to inhibit IFN signaling and counteract host innate antiviral responses by autophagy. IMPORTANCE We show that foot-and-mouth disease virus (FMDV) 3A inhibits retinoic acid-inducible gene I (RIG-I)-like helicase signaling by degrading G3BP1 protein. Furthermore, FMDV 3A reduces G3BP1 by upregulating the expression of autophagy-related protein LRRC25. Additionally, other picornavirus 3A proteins, such as Seneca Valley virus (SVV) 3A, enterovirus 71 (EV71) 3A, and encephalomyocarditis virus (EMCV) 3A, also degrade G3BP1 by upregulating LRRC25 expression. This study will help us improve the design of current vaccines and aid the development of novel control strategies to combat FMD.

scholarly journals Structure and dynamics of the RNAPII CTDsome with Rtt103

2017 ◽  
Vol 114 (42) ◽  
pp. 11133-11138 ◽  
Author(s):  
Olga Jasnovidova ◽  
Tomas Klumpler ◽  
Karel Kubicek ◽  
Sergei Kalynych ◽  
Pavel Plevka ◽  
...  
Keyword(s):  
Rna Polymerase Ii ◽  
Coiled Coil ◽  
Random Coil ◽  
Sequence Complexity ◽  
Structure And Dynamics ◽  
Coiled Coil Domain ◽  
Transcription Termination Factor ◽  
Coil Structure ◽  
Random Coil Structure ◽  
Long Rod

RNA polymerase II contains a long C-terminal domain (CTD) that regulates interactions at the site of transcription. The CTD architecture remains poorly understood due to its low sequence complexity, dynamic phosphorylation patterns, and structural variability. We used integrative structural biology to visualize the architecture of the CTD in complex with Rtt103, a 3′-end RNA-processing and transcription termination factor. Rtt103 forms homodimers via its long coiled-coil domain and associates densely on the repetitive sequence of the phosphorylated CTD via its N-terminal CTD-interacting domain. The CTD–Rtt103 association opens the compact random coil structure of the CTD, leading to a beads-on-a-string topology in which the long rod-shaped Rtt103 dimers define the topological and mobility restraints of the entire assembly. These findings underpin the importance of the structural plasticity of the CTD, which is templated by a particular set of CTD-binding proteins.

scholarly journals Modification of picornavirus genomic RNA using ‘click’ chemistry shows that unlinking of the VPg peptide is dispensable for translation and replication of the incoming viral RNA

2013 ◽  
Vol 42 (4) ◽  
pp. 2473-2482 ◽  
Author(s):  
Martijn A. Langereis ◽  
Qian Feng ◽  
Frank H. T. Nelissen ◽  
Richard Virgen-Slane ◽  
Gerbrand J. van der Heden van Noort ◽  
...  
Keyword(s):  
Click Reaction ◽  
Enterovirus 71 ◽  
Foot And Mouth Disease ◽  
Viral Rna ◽  
Host Protein ◽  
Genomic Rna ◽  
Rna Molecules ◽  
Rna Translation ◽  
Mouth Disease Virus ◽  
Covalently Linked

Abstract Picornaviruses constitute a large group of viruses comprising medically and economically important pathogens such as poliovirus, coxsackievirus, rhinovirus, enterovirus 71 and foot-and-mouth disease virus. A unique characteristic of these viruses is the use of a viral peptide (VPg) as primer for viral RNA synthesis. As a consequence, all newly formed viral RNA molecules possess a covalently linked VPg peptide. It is known that VPg is enzymatically released from the incoming viral RNA by a host protein, called TDP2, but it is still unclear whether the release of VPg is necessary to initiate RNA translation. To study the possible requirement of VPg release for RNA translation, we developed a novel method to modify the genomic viral RNA with VPg linked via a ‘non-cleavable’ bond. We coupled an azide-modified VPg peptide to an RNA primer harboring a cyclooctyne [bicyclo[6.1.0]nonyne (BCN)] by a copper-free ‘click’ reaction, leading to a VPg-triazole-RNA construct that was ‘non-cleavable’ by TDP2. We successfully ligated the VPg-RNA complex to the viral genomic RNA, directed by base pairing. We show that the lack of VPg unlinkase does not influence RNA translation or replication. Thus, the release of the VPg from the incoming viral RNA is not a prerequisite for RNA translation or replication.

N.M.R. studies on myelin basic protein. I. 13C spectra in aqueous solutions

1978 ◽  
Vol 31 (11) ◽  
pp. 2367 ◽  
Author(s):  
BE Chapman ◽  
WJ Moore
Keyword(s):  
Myelin Basic Protein ◽  
Basic Protein ◽  
Polypeptide Chain ◽  
Random Coil ◽  
Side Chain ◽  
Amino Acid Residues ◽  
Native Protein ◽  
Denatured Protein ◽  
Coil Structure ◽  
Random Coil Structure

Carbon-13 n.m.r, spectra have been obtained for bovine myelin basic protein at pD 4.4 in D2O and in 6 M guanidine deuterochloride solutions. Chemical-shift differences between resonances from some amino acid residues are interpreted in terms of structured regions in the polypeptide chain of the native protein, whereas the denatured protein displays the spectrum expected for an essentially random coil. Measurements of T1 and n.O.e. provide quantitative data on the dynamics of the backbone and side-chain carbons, and give support to the conclusion that the native protein does not have a random-coil structure.

scholarly journals Microwave Pretreatment and Enzymolysis Optimization of the Lotus Seed Protein

2019 ◽  
Vol 6 (2) ◽  
pp. 28
Author(s):  
Bi Gohi ◽  
Jinze Du ◽  
Hong-Yan Zeng ◽  
Xiao-ju Cao ◽  
Kai Zou
Keyword(s):  
Secondary Structure ◽  
Seed Protein ◽  
Random Coil ◽  
Degree Of Hydrolysis ◽  
High Power Microwave ◽  
Lotus Seed ◽  
Coil Structure ◽  
Random Coil Structure ◽  
Optimized Conditions ◽  
Power Microwave

Pretreatment with a microwave was conducted before enzymolysis and shown to enhance the enzymolysis, which changed the secondary structure of the lotus seed protein. Under high-power microwave irradiation, sub bonds of the protein were broken, causing disaggregation and unfolding of the secondary structure, namely a decrease in the intermolecular aggregate structure and increase in the random coil structure, making the protein bonds susceptible to papain in the enzymolysis. On the other hand, a response surface methodology (RSM) was launched to investigate the influence of the enzymolysis process variables on the DH (degree of hydrolysis). The statistical analysis revealed that the optimized conditions were a protein substrate concentration of 15 g/L, pH of 5.5, enzymolysis temperature of 57 °C, papain amount of 0.5 g/L, and enzymolysis time of 45 min, for which the predicted value of the DH was 35.64%. The results indicated that a microwave also had better potential for applications in the enzymolysis of foods.

Photoluminescence dynamics of copper nanoclusters synthesized by cellulase: role of the random-coil structure

RSC Advances ◽  
2016 ◽  
Vol 6 (60) ◽  
pp. 55539-55545 ◽  
Author(s):  
Akanksha Singh ◽  
Tripti Rai ◽  
Debashis Panda
Keyword(s):  
Green Emission ◽  
Luminescent Properties ◽  
Random Coil ◽  
Copper Nanoclusters ◽  
Coil Structure ◽  
Random Coil Structure ◽  
Directed Synthesis

Cellulase-directed synthesis of magic numbered Cu NCs with blue-, cyan-, and green emission from Cu12, Cu20, and Cu34, respectively is presented. The random coil structure of enzyme dictates the size and luminescent properties of Cu NCs.

scholarly journals Effects of Picornavirus 3A Proteins on Protein Transport and GBF1-Dependent COP-I Recruitment

2006 ◽  
Vol 80 (23) ◽  
pp. 11852-11860 ◽  
Author(s):  
Els Wessels ◽  
Daniël Duijsings ◽  
Kjerstin H. W. Lanke ◽  
Sander H. J. van Dooren ◽  
Catherine L. Jackson ◽  
...  
Keyword(s):  
Protein Transport ◽  
Hepatitis A Virus ◽  
Foot And Mouth Disease ◽  
Underlying Mechanism ◽  
Encephalomyocarditis Virus ◽  
Nucleotide Exchange ◽  
Guanine Nucleotide Exchange ◽  
Nucleotide Exchange Factor ◽  
Mouth Disease Virus ◽  
The Family

ABSTRACT The 3A protein of the coxsackievirus B3 (CVB3), an enterovirus that belongs to the family of the picornaviruses, inhibits endoplasmic reticulum-to-Golgi transport. Recently, we elucidated the underlying mechanism by showing that CVB3 3A interferes with ADP-ribosylation factor 1 (Arf1)-dependent COP-I recruitment to membranes by binding and inhibiting the function of GBF1, a guanine nucleotide exchange factor that is required for the activation of Arf1 (E. Wessels et al., Dev. Cell 11:191-201, 2006). Here, we show that the 3A protein of poliovirus, another enterovirus, is also able to interfere with COP-I recruitment through the same mechanism. No interference with protein transport or COP-I recruitment was observed for the 3A proteins of any of the other picornaviruses tested here (human rhinovirus [HRV], encephalomyocarditis virus, foot-and-mouth disease virus, and hepatitis A virus). We show that the 3A proteins of HRV, which are the most closely related to the enteroviruses, are unable to inhibit COP-I recruitment, due to a reduced ability to bind GBF1. When the N-terminal residues of the HRV 3A proteins are replaced by those of CVB3 3A, chimeric proteins are produced that have gained the ability to bind GBF1 and, by consequence, to inhibit protein transport. These results show that the N terminus of the CVB3 3A protein is important for binding of GBF1 and its transport-inhibiting function. Taken together, our data demonstrate that the activity of the enterovirus 3A protein to inhibit GBF1-dependent COP-I recruitment is unique among the picornaviruses.

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