scholarly journals The key amino acids of E protein involved in early flavivirus infection: viral entry

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Tao Hu ◽  
Zhen Wu ◽  
Shaoxiong Wu ◽  
Shun Chen ◽  
Anchun Cheng
Keyword(s):  
Amino Acids ◽  
Conformational Changes ◽  
Viral Entry ◽  
Envelope Protein ◽  
Cell Attachment ◽  
Envelope Proteins ◽  
Infection Process ◽  
Early Infection ◽  
Protein Amino Acids ◽  
Α Helix

AbstractFlaviviruses are enveloped viruses that infect multiple hosts. Envelope proteins are the outermost proteins in the structure of flaviviruses and mediate viral infection. Studies indicate that flaviviruses mainly use envelope proteins to bind to cell attachment receptors and endocytic receptors for the entry step. Here, we present current findings regarding key envelope protein amino acids that participate in the flavivirus early infection process. Among these sites, most are located in special positions of the protein structure, such as the α-helix in the stem region and the hinge region between domains I and II, motifs that potentially affect the interaction between different domains. Some of these sites are located in positions involved in conformational changes in envelope proteins. In summary, we summarize and discuss the key envelope protein residues that affect the entry process of flaviviruses, including the process of their discovery and the mechanisms that affect early infection.

scholarly journals Structure-Based Mutational Analysis of Several Sites in the E Protein: Implications for Understanding the Entry Mechanism of Japanese Encephalitis Virus

2015 ◽  
Vol 89 (10) ◽  
pp. 5668-5686 ◽  
Author(s):  
Haibin Liu ◽  
Yi Liu ◽  
Shaobo Wang ◽  
Yanjun Zhang ◽  
Xiangyang Zu ◽  
...  
Keyword(s):  
Amino Acids ◽  
Japanese Encephalitis Virus ◽  
Membrane Fusion ◽  
Japanese Encephalitis ◽  
Receptor Binding ◽  
Viral Entry ◽  
Envelope Protein ◽  
Encephalitis Virus ◽  
Entry Pathway ◽  
Entry Mechanism

ABSTRACTJapanese encephalitis virus (JEV), which causes viral encephalitis in humans, is a serious risk to global public health. The JEV envelope protein mediates the viral entry pathway, including receptor-binding and low-pH-triggered membrane fusion. Utilizing mutagenesis of a JEV infectious cDNA clone, mutations were introduced into the potential receptor-binding motif or into residues critical for membrane fusion in the envelope protein to systematically investigate the JEV entry mechanism. We conducted experiments evaluating infectious particle, recombinant viral particle, and virus-like particle production and found that most mutations impaired virus production. Subcellular fractionation confirmed that five mutations—in I0, ij, BC, and FG and the R9A substitution—impaired virus assembly, and the assembled virus particles of another five mutations—in kl and the E373A, F407A, L221S, and W217A substitutions—were not released into the secretory pathway. Next, we examined the entry activity of six mutations yielding infectious virus. The results showed N154 and the DE loop are not the only or major receptor-binding motifs for JEV entry into BHK-21 cells; four residues, H144, H319, T410, and Q258, participating in the domain I (DI)-DIII interaction or zippering reaction are important to maintain the efficiency of viral membrane fusion. By continuous passaging of mutants, adaptive mutations from negatively charged amino acids to positively charged or neutral amino acids, such as E138K and D389G, were selected and could restore the viral entry activity.IMPORTANCERecently, there has been much interest in the entry mechanism of flaviviruses into host cells, including the viral entry pathway and membrane fusion mechanism. Our study provides strong evidence for the critical role of several residues in the envelope protein in the assembly, release, and entry of JEV, which also contributes to our understanding of the flaviviral entry mechanism. Furthermore, we demonstrate that the H144A, H319A, T410A, and Q258A mutants exhibit attenuated fusion competence, which may be used to develop novel vaccine candidates for flaviviruses.

scholarly journals Calculation and Analysis of Fractal Descriptors for Protein Amino Acids in Various Conformational States

2018 ◽  
Vol 1 (3) ◽  
pp. e00070
Author(s):  
V.Yu. Grigorev ◽  
L.D. Grigoreva
Keyword(s):  
Amino Acids ◽  
Conformational Transition ◽  
Van Der Waals ◽  
Conformational State ◽  
Conformational States ◽  
Protein Amino Acids ◽  
Α Helix ◽  
Β Sheet ◽  
Fractal Descriptor

A series of 20 proteinogenic amino acids was studied. Four types of fractal descriptors for 2 conformational states are calculated: α-helix and 1-strand β-sheet. Based on the analysis of the results obtained, it is established that when the conformational state of the amino acids (α-helix→β-sheet) changes, significant changes in the fractal descriptor Dtot, in the calculation of which all the atoms of the molecule are used, are not observed. However, the more specific descriptors Dval, Dvdw and Dunb, which reflect the aggregate of valence-coupled, van der Waals contact and unbound atoms, respectively, are more sensitive to the conformational transition. The increase Dval, Dvdw and the decrease Dunb values were established for a series of 7 amino acids.

scholarly journals HIV-1 Envelope Glycoprotein at the Interface of Host Restriction and Virus Evasion

Viruses ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 311 ◽  
Author(s):  
Saina Beitari ◽  
Yimeng Wang ◽  
Shan-Lu Liu ◽  
Chen Liang
Keyword(s):  
Viral Infection ◽  
Adaptive Immunity ◽  
Viral Entry ◽  
Envelope Protein ◽  
Envelope Proteins ◽  
Viral Envelope ◽  
Innate Immune ◽  
Host Restriction ◽  
Hiv 1 ◽  
Viral Envelope Proteins

Without viral envelope proteins, viruses cannot enter cells to start infection. As the major viral proteins present on the surface of virions, viral envelope proteins are a prominent target of the host immune system in preventing and ultimately eliminating viral infection. In addition to the well-appreciated adaptive immunity that produces envelope protein-specific antibodies and T cell responses, recent studies have begun to unveil a rich layer of host innate immune mechanisms restricting viral entry. This review focuses on the exciting progress that has been made in this new direction of research, by discussing various known examples of host restriction of viral entry, and diverse viral countering strategies, in particular, the emerging role of viral envelope proteins in evading host innate immune suppression. We will also highlight the effective cooperation between innate and adaptive immunity to achieve the synergistic control of viral infection by targeting viral envelope protein and checking viral escape. Given that many of the related findings were made with HIV-1, we will use HIV-1 as the model virus to illustrate the basic principles and molecular mechanisms on host restriction targeting HIV-1 envelope protein.

scholarly journals Molecular phylogeny and missense mutations of envelope proteins across coronaviruses

2020 ◽  
Author(s):  
Sk Sarif Hassan ◽  
Pabitra Pal Choudhury ◽  
Bidyut Roy
Keyword(s):  
Amino Acids ◽  
Phylogenetic Analysis ◽  
Amino Acid ◽  
Molecular Phylogeny ◽  
Envelope Protein ◽  
Envelope Proteins ◽  
Parental Origin ◽  
Missense Mutations ◽  
E Proteins ◽  
Complete Genomes

Envelope protein is one of the structural viroporins (76–109 amino acids) present in the coronavirus. Sixteen sequentially different E proteins were observed from a total of 4917 available complete genomes as on 18th June, 2020 in the NCBI database. The missense mutations over the envelope protein across various coronaviruses of the $\beta$-genus were analyzed to know the immediate parental origin of the envelope protein of SARS-CoV2. The evolutionary origin is also endorsed by the phylogenetic analysis of the envelope proteins comparing sequence homology as well as amino acid conservations.

scholarly journals Environmental Dependence of the Structure of the C-terminal Domain of the SARS-CoV-2 Envelope Protein

2020 ◽  
Author(s):  
Kundlik Gadhave ◽  
Ankur Kumar ◽  
Prateek Kumar ◽  
Shivani K. Kapuganti ◽  
Neha Garg ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Envelope Protein ◽  
Cell Membranes ◽  
Infection Process ◽  
Structural Basis ◽  
List Type ◽  
Ordered Structure ◽  
Prolonged Incubation ◽  
Intrinsically Disordered ◽  
Terminal Domain

AbstractThe SARS-CoV-2 envelope protein (E) is involved in a broad spectrum of functions in the cycle of the virus, including assembly, budding, envelope formation, and pathogenesis. To enable these activities, E is likely to be capable of changing its conformation depending on environmental cues. To investigate this issue, here we characterised the structural properties of the C-terminal domain of E (E-CTD), which has been reported to interact with host cell membranes. We first studied the conformation of the E-CTD in solution, finding characteristic features of a disordered protein. By contrast, in the presence of large unilamellar vesicles and micelles, which mimic cell membranes, the E-CTD was observed to become structured. The E-CTD was also found to display conformational changes with osmolytes. Furthermore, prolonged incubation of the E-CTD under physiological conditions resulted in amyloid-like fibril formation. Taken together, these findings indicate that the E-CTD can change its conformation depending on its environment, ranging from a disordered state, to a membrane-bound folded state, and an amyloid state. Our results thus provide insight into the structural basis of the role of E in the viral infection process.HighlightsThe E-CTD of SARS-CoV-2 is intrinsically disordered in solutionThe E-CTD folds into an ordered structure in presence of membrane mimeticsThe E-CTD displays conformational changes in the presence of osmolytesProlonged incubation of the E-CTD leads to its self-assembly into amyloid-like fibrilsGraphical AbstractStructural heterogeneity of the E-CTD.The E-CTD shows a disordered secondary structure in an aqueous solution and converts into an ordered structure in the presence of membrane mimetics (neutral and negative lipids) and natural osmolytes (TMAO). Incubation at physiological condition shows typical amyloid-like fibrils. The yellow-colored structure represents a predicted structure of the E-CTD by PEP-FOLD.

scholarly journals Repositioning of Ligands That Target the Spike Glycoprotein as Potential Drugs for SARS-CoV-2 in an In Silico Study

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5615
Author(s):  
Gema Lizbeth Ramírez-Salinas ◽  
Marlet Martínez-Archundia ◽  
José Correa-Basurto ◽  
Jazmín García-Machorro
Keyword(s):  
Amino Acids ◽  
Conformational Changes ◽  
Viral Entry ◽  
Drug Repositioning ◽  
Specific Treatment ◽  
Binding Motif ◽  
Spike Glycoprotein ◽  
Pharmacological Agents ◽  
Docking Simulations ◽  
Approved Drugs

The worldwide health emergency of the SARS-CoV-2 pandemic and the absence of a specific treatment for this new coronavirus have led to the use of computational strategies (drug repositioning) to search for treatments. The aim of this work is to identify FDA (Food and Drug Administration)-approved drugs with the potential for binding to the spike structural glycoprotein at the hinge site, receptor binding motif (RBM), and fusion peptide (FP) using molecular docking simulations. Drugs that bind to amino acids are crucial for conformational changes, receptor recognition, and fusion of the viral membrane with the cell membrane. The results revealed some drugs that bind to hinge site amino acids (varenicline, or steroids such as betamethasone while other drugs bind to crucial amino acids in the RBM (naldemedine, atovaquone, cefotetan) or FP (azilsartan, maraviroc, and difluprednate); saquinavir binds both the RBM and the FP. Therefore, these drugs could inhibit spike glycoprotein and prevent viral entry as possible anti-COVID-19 drugs. Several drugs are in clinical studies; by focusing on other pharmacological agents (candesartan, atovaquone, losartan, maviroc and ritonavir) in this work we propose an additional target: the spike glycoprotein. These results can impact the proposed use of treatments that inhibit the first steps of the virus replication cycle.

scholarly journals The Pre-S1 and Antigenic Loop Infectivity Determinants of the Hepatitis B Virus Envelope Proteins Are Functionally Independent

2009 ◽  
Vol 83 (23) ◽  
pp. 12443-12451 ◽  
Author(s):  
Yann Le Duff ◽  
Matthieu Blanchet ◽  
Camille Sureau
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Viral Entry ◽  
Envelope Protein ◽  
Envelope Proteins ◽  
Viral Envelope ◽  
Dominant Negative ◽  
Dominant Negative Effect ◽  
Receptor Binding Site ◽  
B Virus

ABSTRACT The hepatitis B virus (HBV) envelope proteins bear two determinants of viral entry: a receptor-binding site (RBS) in the pre-S1 domain of the large envelope protein and a conformation-dependent determinant, of unknown function, in the antigenic loop (AGL) of the small, middle, and large envelope proteins. Using an in vitro infection assay consisting of susceptible HepaRG cells and the hepatitis delta virus (HDV) as a surrogate of HBV, we first investigated whether subelements of the pre-S1 determinant (amino acids 2 to 75), i.e., the N-terminal myristoyl anchor, subdomain 2-48 (RBS), and subdomain 49-75, were functionally separable. In transcomplementation experiments, coexpression of two distinct infectivity-deficient pre-S1 mutants at the surface of HDV virions failed to restore infectivity, indicating that the myristoyl anchor, the 2-48 RBS, and the 49-75 sequence, likely cooperate in cis at viral entry. Furthermore, we showed that as much as 52% of total pre-S1 in the HDV envelope could bear infectivity-deficient lesions without affecting entry, indicating that a small number of pre-S1 polypeptides—estimated at three to four per virion—is sufficient for infectivity. We next investigated the AGL activity in the small or large envelope protein background (S- and L-AGL, respectively) and found that lesions in S-AGL were more deleterious to infectivity than in L-AGL, a difference that reflects the relative stoichiometry of the small and large envelope proteins in the viral envelope. Finally, we showed that C147S, an AGL infectivity-deficient substitution, exerted a dominant-negative effect on infectivity, likely reflecting an involvement of C147 in intermolecular disulfide bonds.

scholarly journals Nanostructure of bioactive glass affects bone cell attachment via protein restructuring upon adsorption

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ukrit Thamma ◽  
Tia J. Kowal ◽  
Matthias M. Falk ◽  
Himanshu Jain
Keyword(s):  
Bioactive Glass ◽  
Cell Response ◽  
Interfacial Layer ◽  
Cell Attachment ◽  
Bone Cell ◽  
Nano Structure ◽  
Rgd Sequence ◽  
Engineered Tissue ◽  
Α Helix ◽  
Β Sheet

AbstractThe nanostructure of engineered bioscaffolds has a profound impact on cell response, yet its understanding remains incomplete as cells interact with a highly complex interfacial layer rather than the material itself. For bioactive glass scaffolds, this layer comprises of silica gel, hydroxyapatite (HA)/carbonated hydroxyapatite (CHA), and absorbed proteins—all in varying micro/nano structure, composition, and concentration. Here, we examined the response of MC3T3-E1 pre-osteoblast cells to 30 mol% CaO–70 mol% SiO2 porous bioactive glass monoliths that differed only in nanopore size (6–44 nm) yet resulted in the formation of HA/CHA layers with significantly different microstructures. We report that cell response, as quantified by cell attachment and morphology, does not correlate with nanopore size, nor HA/CHO layer micro/nano morphology, or absorbed protein amount (bovine serum albumin, BSA), but with BSA’s secondary conformation as indicated by its β-sheet/α-helix ratio. Our results suggest that the β-sheet structure in BSA interacts electrostatically with the HA/CHA interfacial layer and activates the RGD sequence of absorbed adhesion proteins, such as fibronectin and vitronectin, thus significantly enhancing the attachment of cells. These findings provide new insight into the interaction of cells with the scaffolds’ interfacial layer, which is vital for the continued development of engineered tissue scaffolds.

scholarly journals Nectar non-protein amino acids (NPAAs) do not change nectar palatability but enhance learning and memory in honey bees

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Daniele Carlesso ◽  
Stefania Smargiassi ◽  
Elisa Pasquini ◽  
Giacomo Bertelli ◽  
David Baracchi
Keyword(s):  
Amino Acids ◽  
Learning And Memory ◽  
Honey Bees ◽  
Feeding Preference ◽  
Memory Retention ◽  
Floral Nectar ◽  
Olfactory Conditioning ◽  
Specific Memory ◽  
Protein Amino Acids ◽  
Valuable Compounds

AbstractFloral nectar is a pivotal element of the intimate relationship between plants and pollinators. Nectars are composed of a plethora of nutritionally valuable compounds but also hundreds of secondary metabolites (SMs) whose function remains elusive. Here we performed a set of behavioural experiments to study whether five ubiquitous nectar non-protein amino acids (NPAAs: β-alanine, GABA, citrulline, ornithine and taurine) interact with gustation, feeding preference, and learning and memory in Apis mellifera. We showed that foragers were unable to discriminate NPAAs from water when only accessing antennal chemo-tactile information and that freely moving bees did not exhibit innate feeding preferences for NPAAs. Also, NPAAs did not alter food consumption or longevity in caged bees over 10 days. Taken together our data suggest that natural concentrations of NPAAs did not alter nectar palatability to bees. Olfactory conditioning assays showed that honey bees were more likely to learn a scent when it signalled a sucrose reward containing either β-alanine or GABA, and that GABA enhanced specific memory retention. Conversely, when ingested two hours prior to conditioning, GABA, β-alanine, and taurine weakened bees’ acquisition performances but not specific memory retention, which was enhanced in the case of β-alanine and taurine. Neither citrulline nor ornithine affected learning and memory. NPAAs in nectars may represent a cooperative strategy adopted by plants to attract beneficial pollinators.

Protection of Italian ryegrass (Lolium multiflorum L.) seedlings from salinity stress following seed priming with L-methionine and casein hydrolysate

2020 ◽  
pp. 1-9
Author(s):  
Keum-Ah Lee ◽  
Youngnam Kim ◽  
Hossein Alizadeh ◽  
David W.M. Leung
Keyword(s):  
Oxidative Stress ◽  
Amino Acids ◽  
Salinity Stress ◽  
Lolium Multiflorum ◽  
Casein Hydrolysate ◽  
Seed Priming ◽  
Germination Percentage ◽  
Italian Ryegrass ◽  
Significant Difference ◽  
Protein Amino Acids

Abstract Seed priming with water (hydropriming or HP) has been shown to be beneficial for seed germination and plant growth. However, there is little information on the effects of seed priming with amino acids and casein hydrolysate (CH) compared with HP, particularly in relation to early post-germinative seedling growth under salinity stress. In this study, Italian ryegrass seeds (Lolium multiflorum L.) were primed with 1 mM of each of the 20 protein amino acids and CH (200 mg l−1) before they were germinated in 0, 60 and 90 mM NaCl in Petri dishes for 4 d in darkness. Germination percentage (GP), radicle length (RL) and peroxidase (POD) activity in the root of 4-d-old Italian ryegrass seedlings were investigated. Generally, when the seeds were germinated in 0, 60 and 90 mM NaCl, there was no significant difference in GP of seeds among various priming treatments, except that a higher GP was observed in seeds of HP treatment compared with the non-primed seeds when incubated in 60 mM NaCl. When incubated in 60 and 90 mM NaCl, seedlings from seeds primed with L-methionine or CH exhibited greater RL (greater protection against salinity stress) and higher root POD activity than those from non-primed and hydro-primed seeds. Under salinity stress, there were higher levels of malondialdehyde (MDA) in the root of 4-d-old Italian ryegrass seedlings, a marker of oxidative stress, but seed priming with CH was effective in reducing the salinity-triggered increase in MDA content. These results suggest that priming with L-methionine or CH would be better than HP for the protection of seedling root growth under salinity stress and might be associated with enhanced antioxidative defence against salinity-induced oxidative stress.

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