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https://www.readbyqxmd.com/read/28346455/collective-helicity-switching-of-a-dna-coat-assembly
#1
Yongju Kim, Huichang Li, Ying He, Xi Chen, Xiaoteng Ma, Myongsoo Lee
Hierarchical assemblies of biomolecular subunits can carry out versatile tasks at the cellular level with remarkable spatial and temporal precision. As an example, the collective motion and mutual cooperation between complex protein machines mediate essential functions for life, such as replication, synthesis, degradation, repair and transport. Nucleic acid molecules are far less dynamic than proteins and need to bind to specific proteins to form hierarchical structures. The simplest example of these nucleic acid-based structures is provided by a rod-shaped tobacco mosaic virus, which consists of genetic material surrounded by coat proteins...
March 27, 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/28345819/outbreak-investigations-and-molecular-characterization-of-foot-and-mouth-disease-viruses-circulating-in-south-west-niger
#2
B Souley Kouato, F M Elliot, D P King, J Hyera, N J Knowles, A B Ludi, V Mioulet, G Matlho, K De Clercq, E Thys, H Marichatou, S Issa, C Saegerman
In Niger, the epidemiological situation regarding foot-and-mouth disease is unclear as many outbreaks are unreported. This study aimed (i) to identify Foot-and-mouth disease virus (FMDV) strains currently circulating in cattle herds, and (ii) to identify risk factors associated with Foot-and-mouth disease (FMD)-seropositive animals in clinical outbreaks. Epithelial tissues (n = 25) and sera (n = 227) were collected from cattle in eight districts of the south-western part of Niger. Testing of clinical material revealed the presence of FMDV serotype O that was characterized within the O/WEST AFRICA topotype...
March 27, 2017: Transboundary and Emerging Diseases
https://www.readbyqxmd.com/read/28345656/structure-and-function-of-the-zika-virus-full-length-ns5-protein
#3
Baoyu Zhao, Guanghui Yi, Fenglei Du, Yin-Chih Chuang, Robert C Vaughan, Banumathi Sankaran, C Cheng Kao, Pingwei Li
The recent outbreak of Zika virus (ZIKV) has infected over 1 million people in over 30 countries. ZIKV replicates its RNA genome using virally encoded replication proteins. Nonstructural protein 5 (NS5) contains a methyltransferase for RNA capping and a polymerase for viral RNA synthesis. Here we report the crystal structures of full-length NS5 and its polymerase domain at 3.0 Å resolution. The NS5 structure has striking similarities to the NS5 protein of the related Japanese encephalitis virus. The methyltransferase contains in-line pockets for substrate binding and the active site...
March 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28345600/the-structure-of-zika-virus-ns5-reveals-a-conserved-domain-conformation
#4
Boxiao Wang, Xiao-Feng Tan, Stephanie Thurmond, Zhi-Min Zhang, Asher Lin, Rong Hai, Jikui Song
The recent outbreak of Zika virus (ZIKV) has imposed a serious threat to public health. Here we report the crystal structure of the ZIKV NS5 protein in complex with S-adenosyl-L-homocysteine, in which the tandem methyltransferase (MTase) and RNA-dependent RNA polymerase (RdRp) domains stack into one of the two alternative conformations of flavivirus NS5 proteins. The activity of this NS5 protein is verified through a de novo RdRp assay on a subgenomic ZIKV RNA template. Importantly, our structural analysis leads to the identification of a potential drug-binding site of ZIKV NS5, which might facilitate the development of novel antivirals for ZIKV...
March 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28345596/crystal-structure-of-zika-virus-ns5-rna-dependent-rna-polymerase
#5
Andre S Godoy, Gustavo M A Lima, Ketllyn I Z Oliveira, Naiara U Torres, Fernando V Maluf, Rafael V C Guido, Glaucius Oliva
The current Zika virus (ZIKV) outbreak became a global health threat of complex epidemiology and devastating neurological impacts, therefore requiring urgent efforts towards the development of novel efficacious and safe antiviral drugs. Due to its central role in RNA viral replication, the non-structural protein 5 (NS5) RNA-dependent RNA-polymerase (RdRp) is a prime target for drug discovery. Here we describe the crystal structure of the recombinant ZIKV NS5 RdRp domain at 1.9 Å resolution as a platform for structure-based drug design strategy...
March 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28344575/identification-of-capsid-coat-related-protein-folds-and-their-utility-for-virus-classification
#6
Arshan Nasir, Gustavo Caetano-Anollés
The viral supergroup includes the entire collection of known and unknown viruses that roam our planet and infect life forms. The supergroup is remarkably diverse both in its genetics and morphology and has historically remained difficult to study and classify. The accumulation of protein structure data in the past few years now provides an excellent opportunity to re-examine the classification and evolution of viruses. Here we scan completely sequenced viral proteomes from all genome types and identify protein folds involved in the formation of viral capsids and virion architectures...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28344321/broad-spectrum-antiviral-activity-for-paramyxoviruses-is-modulated-by-biophysical-properties-of-fusion-inhibitory-peptides
#7
Cyrille Mathieu, Marcelo T Augusto, Stefan Niewiesk, Branka Horvat, Laura M Palermo, Giuseppina Sanna, Silvia Madeddu, Devra Huey, Miguel A R B Castanho, Matteo Porotto, Nuno C Santos, Anne Moscona
Human paramyxoviruses include global causes of lower respiratory disease like the parainfluenza viruses, as well as agents of lethal encephalitis like Nipah virus. Infection is initiated by viral glycoprotein-mediated fusion between viral and host cell membranes. Paramyxovirus viral fusion proteins (F) insert into the target cell membrane, and form a transient intermediate that pulls the viral and cell membranes together as two heptad-repeat regions refold to form a six-helix bundle structure that can be specifically targeted by fusion-inhibitory peptides...
March 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28343993/discovering-key-residues-of-dengue-virus-ns2b-ns3-protease-new-binding-sites-for-antiviral-inhibitors-design
#8
D Aguilera-Pesantes, L E Robayo, P E Méndez, D Mollocana, Y Marrero-Ponce, F J Torres, M A Méndez
The NS2B-NS3 protease is essential for the Dengue Virus (DENV) replication process. This complex constitutes a target for efficient antiviral discovery because a drug could inhibit the viral polyprotein processing. Furthermore, since the protease is highly conserved between the four Dengue virus serotypes, it is probable that a drug would be equally effective against all of them. In this article, a strategy is reported that allowed us to identify influential residues on the function of the Dengue NS2b-NS3 Protease...
March 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28341122/molecular-dynamics-simulations-of-zika-virus-ns3-helicase-insights-into-rna-binding-site-activity
#9
Melina Mottin, Rodolpho C Braga, Roosevelt A da Silva, Joao H Martins da Silva, Alexander L Perryman, Sean Ekins, Carolina Horta Andrade
America is still suffering with the outbreak of Zika virus (ZIKV) infection. Congenital ZIKV syndrome has already caused a public health emergency of international concern. However, there are still no vaccines to prevent or drugs to treat the infection caused by ZIKV. The ZIKV NS3 helicase (NS3h) protein is a promising target for drug discovery due to its essential role in viral genome replication. NS3h unwinds the viral RNA to enable the replication of the viral genome by the NS5 protein. NS3h contains two important binding sites: the NTPase binding site and the RNA binding site...
March 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28340349/structure-reveals-mechanisms-of-viral-suppressors-that-intercept-a-crispr-rna-guided-surveillance-complex
#10
Saikat Chowdhury, Joshua Carter, MaryClare F Rollins, Sarah M Golden, Ryan N Jackson, Connor Hoffmann, Lyn'Al Nosaka, Joseph Bondy-Denomy, Karen L Maxwell, Alan R Davidson, Elizabeth R Fischer, Gabriel C Lander, Blake Wiedenheft
Genetic conflict between viruses and their hosts drives evolution and genetic innovation. Prokaryotes evolved CRISPR-mediated adaptive immune systems for protection from viral infection, and viruses have evolved diverse anti-CRISPR (Acr) proteins that subvert these immune systems. The adaptive immune system in Pseudomonas aeruginosa (type I-F) relies on a 350 kDa CRISPR RNA (crRNA)-guided surveillance complex (Csy complex) to bind foreign DNA and recruit a trans-acting nuclease for target degradation. Here, we report the cryo-electron microscopy (cryo-EM) structure of the Csy complex bound to two different Acr proteins, AcrF1 and AcrF2, at an average resolution of 3...
March 23, 2017: Cell
https://www.readbyqxmd.com/read/28339926/study-on-the-expression-of-human-lysozyme-in-oviduct-bioreactor-mediated-by-recombinant-avian-adeno-associated-virus1
#11
A P Wang, Y J Wang, S Wu, W Y Zuo, C M Guo, W M Hong, S Y Zhu
Due to its antimicrobial properties and low toxicity, human lysozyme (hLYZ) has broad application in the medical field and as a preservative used by the food industry. However, limited availability hinders its widespread use. Hence, we constructed a recombinant avian adeno-associated virus (rAAAV) that would specifically express hLYZ in the chicken oviduct and harvested hLYZ from the egg whites of laying hens. The oviduct-specific human lysozyme expression cassette flanked by avian adeno-associated virus (AAAV) inverted terminal repeats (ITRs) was subcloned into the modified baculovirus transfer vector pFBX, and then the recombinant baculovirus rBac-ITRLYZ was generated...
March 2, 2017: Poultry Science
https://www.readbyqxmd.com/read/28339215/discovery-and-pre-clinical-characterization-of-a-3-rd-generation-4-h-heteroaryldihydropyrimidine-hap-analogues-as-hepatitis-b-virus-hbv-capsid-inhibitors
#12
Zongxing Qiu, Xianfeng Lin, Weixing Zhang, Mingwei Zhou, Lei Guo, Buelent Kocer, Guolong Wu, Zhisen Zhang, Haixia Liu, Houguang Shi, Buyu Kou, Taishan Hu, Yimin Hu, Mengwei Huang, S Frank Yan, Zhiheng Xu, Zheng Zhou, Ning Qin, Yue Fen Wang, Shuang Ren, Hongxia Qiu, Yuxia Zhang, Yi Zhang, Xiaoyue Wu, Kai Sun, Sheng Zhong, Jianxun Xie, Giorgio Ottaviani, Yuan Zhou, Lina Zhu, Xiaojun Tian, Liping Shi, Fang Shen, Yi Mao, Xue Zhou, Lu Gao, John A T Young, Jim Zhen Wu, Guang Yang, Alexander V Mayweg, Hong C Shen, Guozhi Tang, Wei Zhu
Described herein are the discovery and structure-activity relationship (SAR) studies of the 3(rd) generation 4-H heteroaryldihydropyrimidines (4-H HAPs) featuring the introduction of a C6 carboxyl group as novel HBV capsid inhibitors. This new series of 4-H HAPs showed improved anti-HBV activity and better drug-like properties compared to the 1(st) and 2(nd) generation 4-H HAPs. X-ray crystallographic study of analogue 12 (HAP_R01) with Cp149 Y132A mutant hexamer clearly elucidated the role of C6 carboxyl group played for the increased binding affinity, which formed strong hydrogen bonding interactions with capsid protein and coordinated waters...
March 24, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28336404/mapping-region-of-human-restriction-factor-apobec3h-critical-for-interaction-with-hiv-1-vif
#13
Masaaki Nakashima, Shinya Tsuzuki, Hiroaki Awazu, Akiko Hamano, Ayaka Okada, Hirotaka Ode, Masami Maejima, Atsuko Hachiya, Yoshiyuki Yokomaku, Nobuhisa Watanabe, Hirofumi Akari, Yasumasa Iwatani
The APOBEC3 (A3) family of cellular cytidine deaminases comprises seven members (A, B, C, D, F, G, and H) that potently inhibit retroviral replication. Human immunodeficiency virus type 1 (HIV-1) Vif is a small pleiotropic protein that specifically inactivates these enzymes, targeting them for ubiquitin-mediated proteasomal degradation. A3 Vif-interaction sites are presumed to fall into three distinct types: A3C/D/F, A3G, and A3H. To date, two types of A3G and A3C/D/F sites have been well characterized, whereas the A3H Vif-binding site remains poorly defined...
March 20, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28335410/non-canonical-roles-of-dengue-virus-non-structural-proteins
#14
REVIEW
Julianna D Zeidler, Lorena O Fernandes-Siqueira, Glauce M Barbosa, Andrea T Da Poian
The Flaviviridae family comprises a number of human pathogens, which, although sharing structural and functional features, cause diseases with very different outcomes. This can be explained by the plurality of functions exerted by the few proteins coded by viral genomes, with some of these functions shared among members of a same family, but others being unique for each virus species. These non-canonical functions probably have evolved independently and may serve as the base to the development of specific therapies for each of those diseases...
March 13, 2017: Viruses
https://www.readbyqxmd.com/read/28334864/coordination-among-tertiary-base-pairs-results-in-an-efficient-frameshift-stimulating-rna-pseudoknot
#15
Yu-Ting Chen, Kai-Chun Chang, Hao-Teng Hu, Yi-Lan Chen, You-Hsin Lin, Chiung-Fang Hsu, Cheng-Fu Chang, Kung-Yao Chang, Jin-Der Wen
Frameshifting is an essential process that regulates protein synthesis in many viruses. The ribosome may slip backward when encountering a frameshift motif on the messenger RNA, which usually contains a pseudoknot structure involving tertiary base pair interactions. Due to the lack of detailed molecular explanations, previous studies investigating which features of the pseudoknot are important to stimulate frameshifting have presented diverse conclusions. Here we constructed a bimolecular pseudoknot to dissect the interior tertiary base pairs and used single-molecule approaches to assess the structure targeted by ribosomes...
February 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28331984/structure-of-the-n-glycans-from-the-chlorovirus-ne-jv-1
#16
Immacolata Speciale, Irina Agarkova, Garry A Duncan, James L Van Etten, Cristina De Castro
Results from recent studies are breaking the paradigm that all viruses depend on their host machinery to glycosylate their proteins. Chloroviruses encode several genes involved in glycan biosynthesis and some of their capsid proteins are decorated with N-linked oligosaccharides with unique features. Here we describe the elucidation of the N-glycan structure of an unusual chlorovirus, NE-JV-1, that belongs to the Pbi group. The host for NE-JV-1 is the zoochlorella Micractinium conductrix. Spectroscopic analyses established that this N-glycan consists of a core region that is conserved in all of the chloroviruses...
March 22, 2017: Antonie Van Leeuwenhoek
https://www.readbyqxmd.com/read/28331093/structural-characterization-of-hcov-nl63-n-protein
#17
Bozena Szelazek, Wojciech Kabala, Krzysztof Kus, Michal Zdzalik, Aleksandra Twarda-Clapa, Przemyslaw Golik, Michal Burmistrz, Dominik Florek, Benedykt Wladyka, Krzysztof Pyrc, Grzegorz Dubin
Coronaviruses are responsible for upper and lower respiratory tract infections in humans. It is estimated that 1-10% of the population suffers annually from cold-like symptoms related to infection with HCoV-NL63, an alphacoronavirus. The nucleocapsid (N) protein, the major structural component of the capsid, facilitates RNA packing, links the capsid to the envelope and is also involved in multiple other processes including viral replication and evasion of the immune system. Although the role of N protein in viral replication is relatively well described, no structural data are currently available regarding the N proteins of alphacoronaviruses...
March 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28331084/structural-insights-into-emerging-pediatric-pathogens-human-bocaparvoviruses
#18
Mario Mietzsch, Shweta Kailasan, Jamie Garrison, Maria Ilyas, Paul Chipman, Kalle Kantola, Mandy E Janssen, John Spear, Duncan Sousa, Robert McKenna, Kevin Brown, Maria Söderlund-Venermo, Timothy Baker, Mavis Agbandje-McKenna
Bocaparvoviruses are emerging pathogens of the Parvoviridae family. Human bocaviruses 1 (HBoV1) causes severe respiratory infections and HBoV2-4 gastrointestinal infections in young children. Recent reports of life threatening cases, lack of direct treatment or vaccination, and a limited understanding of their disease mechanisms demand the need to study these pathogens on a molecular and structural level for the development of therapeutics. Towards this end, the capsid structures of HBoV1, HBoV3, and HBoV4 were determined to 2...
March 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28330747/m-protein-is-sufficient-for-assembly-and-release-of-peste-des-petits-ruminants-virus-like-particles
#19
Qiuxia Wang, Changbo Ou, Yongxi Dou, Lei Chen, Xuelian Meng, Xingyou Liu, Yan Yu, Jinqing Jiang, Jinyou Ma, Zhidong Zhang, Jianhe Hu, Xuepeng Cai
Peste des petits ruminants virus (PPRV), belonging to paramyxoviruses, has six structure proteins (such as matrix protein (M), nucleocapsid proteins (N), fusion protein (F) and hemagglutinin protein (H)) and could cause high morbidity and mortality in sheep and goats. Although a vaccine strain of PPRV has been rescued and co-expression of M and N could yield PPRV-like particles, the roles of structure proteins in virion assembly and release have not been investigated in detail. In this study, plasmids carrying PPRV cDNA sequences encoding the N, M, H, and F proteins were expressed in Vero cells...
March 18, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28330163/probing-an-optimal-class-distribution-for-enhancing-prediction-and-feature-characterization-of-plant-virus-encoded-rna-silencing-suppressors
#20
Abhigyan Nath, Karthikeyan Subbiah
To counter the host RNA silencing defense mechanism, many plant viruses encode RNA silencing suppressor proteins. These groups of proteins share very low sequence and structural similarities among them, which consequently hamper their annotation using sequence similarity-based search methods. Alternatively the machine learning-based methods can become a suitable choice, but the optimal performance through machine learning-based methods is being affected by various factors such as class imbalance, incomplete learning, selection of inappropriate features, etc...
June 2016: 3 Biotech
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