Abstract:
:Enveloped viruses require viral fusion proteins to promote fusion of the viral envelope with a target cell membrane. To drive fusion, these proteins undergo large conformational changes that must occur at the right place and at the right time. Understanding the elements which control the stability of the prefusion state and the initiation of conformational changes is key to understanding the function of these important proteins. The construction of mutations in the fusion protein transmembrane domains (TMDs) or the replacement of these domains with lipid anchors has implicated the TMD in the fusion process. However, the structural and molecular details of the role of the TMD in these fusion events remain unclear. Previously, we demonstrated that isolated paramyxovirus fusion protein TMDs associate in a monomer-trimer equilibrium, using sedimentation equilibrium analytical ultracentrifugation. Using a similar approach, the work presented here indicates that trimeric interactions also occur between the fusion protein TMDs of Ebola virus, influenza virus, severe acute respiratory syndrome coronavirus (SARS CoV), and rabies virus. Our results suggest that TM-TM interactions are important in the fusion protein function of diverse viral families.IMPORTANCE Many important human pathogens are enveloped viruses that utilize membrane-bound glycoproteins to mediate viral entry. Factors that contribute to the stability of these glycoproteins have been identified in the ectodomain of several viral fusion proteins, including residues within the soluble ectodomain. Although it is often thought to simply act as an anchor, the transmembrane domain of viral fusion proteins has been implicated in protein stability and function as well. Here, using a biophysical approach, we demonstrated that the fusion protein transmembrane domains of several deadly pathogens-Ebola virus, influenza virus, SARS CoV, and rabies virus-self-associate. This observation across various viral families suggests that transmembrane domain interactions may be broadly relevant and serve as a new target for therapeutic development.
journal_name
mSpherejournal_title
mSphereauthors
Webb SR,Smith SE,Fried MG,Dutch REdoi
10.1128/mSphere.00047-18subject
Has Abstractpub_date
2018-04-18 00:00:00issue
2issn
2379-5042pii
3/2/e00047-18journal_volume
3pub_type
杂志文章相关文献
mSphere文献大全abstract::Trichomonas vaginalis is the causative agent of trichomoniasis, the most prevalent nonviral sexually transmitted infection worldwide. Repetitive elements, including transposable elements (TEs) and virally derived repeats, comprise more than half of the ∼160-Mb T. vaginalis genome. An intriguing question is how the par...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.01061-20
更新日期:2021-01-06 00:00:00
abstract::The Paracoccidioides genus includes two species of thermally dimorphic fungi that cause paracoccidioidomycosis, a neglected health-threatening human systemic mycosis endemic to Latin America. To examine the genome evolution and the diversity of Paracoccidioides spp., we conducted whole-genome sequencing of 31 isolates...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00213-16
更新日期:2016-09-28 00:00:00
abstract::Malaria is a devastating illness that causes approximately 500,000 deaths annually. The malaria-causing parasite (Plasmodium genus) uses the process of translational repression to regulate its growth, development, and transmission. As poly(A)-binding proteins (PABP) have been identified as critical components of RNA m...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00435-17
更新日期:2018-01-10 00:00:00
abstract::This study was carried out to evaluate hypotheses generated by fundamental cause theory regarding the socioeconomic status (SES) gradient in colonization with Staphylococcus aureus among Hispanic and non-Hispanic adults living in a border community. Participants (n = 613) recruited in naturally occurring small groups ...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00623-20
更新日期:2020-09-30 00:00:00
abstract::Members of family Coronaviridae cause a variety of diseases in birds and mammals. Porcine hemagglutinating encephalomyelitis virus (PHEV), a lesser-researched coronavirus, can infect naive pigs of any age, but clinical disease is observed in pigs ≤4 weeks of age. No commercial PHEV vaccines are available, and neonatal...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00199-20
更新日期:2020-05-06 00:00:00
abstract::Lassa virus (LASV), a member of the family Arenaviridae, is the causative agent of Lassa fever. Lassa virus is endemic in West African countries, such as Nigeria, Guinea, Liberia, and Sierra Leone, and causes outbreaks annually. Lassa fever onset begins with "flu-like" symptoms and may develop into lethal hemorrhagic ...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00428-19
更新日期:2019-09-25 00:00:00
abstract::Molecular detection of biological agents in the field has traditionally relied on the use of quantitative real-time PCR (qPCR), which now includes commercially available instruments that can be used in the laboratory or field. Adapting this technology for field-forward applications necessitated innovation to minimize ...
journal_title:mSphere
pub_type: 杂志文章,评审
doi:10.1128/mSphere.00695-19
更新日期:2019-12-11 00:00:00
abstract::Many coronavirus disease 2019 (COVID-19) patients demonstrate lethal respiratory complications caused by cytokine release syndrome (CRS). Multiple cytokines have been implicated in CRS, but levels of tumor necrosis factor superfamily 14 (TNFSF14) (LIGHT) have not been previously measured in this setting. In this study...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00699-20
更新日期:2020-08-12 00:00:00
abstract::Various Lactobacillus species have been reported to deconjugate bile acids in the gastrointestinal tract (GIT) through the action of bile salt hydrolase (BSH) proteins. This function contributes to altering the gut microbiota composition and bile metabolism and detoxification and to lowering cholesterol levels. Here, ...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00140-18
更新日期:2018-05-30 00:00:00
abstract::Newborns are constantly exposed to various microbes from birth; hence, diverse commensal bacteria colonize the oral cavity. However, how or when these bacteria construct a complex and stable ecosystem remains unclear. This prospective cohort study examined the temporal changes in bacterial diversity and composition in...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00187-19
更新日期:2019-05-29 00:00:00
abstract::The Anabaena organismic unit is a filament of communicating cells. Under conditions of nitrogen scarcity, some cells along the filament differentiate into heterocysts, which are specialized in the fixation of atmospheric N2 and provide the vegetative cells with N2 fixation products. At a certain stage, the differentia...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00188-20
更新日期:2020-05-20 00:00:00
abstract::Antibiotic resistance has become a major public health concern as bacteria evolve to evade drugs, leading to recurring infections and a decrease in antibiotic efficacy. Systematic efforts have revealed mechanisms involved in resistance. Yet, in many cases, how these specific mechanisms accelerate or slow the evolution...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.01056-20
更新日期:2020-12-16 00:00:00
abstract::Candida albicans is an opportunistic human fungal pathogen that causes superficial fungal infections and lethal systemic infections. To colonize and establish infections, C. albicans coordinates the expression of virulence and metabolic genes. Previous work showed that the homeodomain transcription factor Grf10 is req...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00161-17
更新日期:2017-08-02 00:00:00
abstract::The facultative anaerobic polymorphic fungus Candida albicans and the strictly anaerobic Gram-positive bacterium Clostridium difficile are two opportunistic pathogens residing in the human gut. While a few studies have focused on the prevalence of C. albicans in C. difficile-infected patients, the nature of the intera...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00187-16
更新日期:2016-11-09 00:00:00
abstract::Although the role of high-risk human papillomaviruses (hrHPVs) as etiological agents in cancer development has been intensively studied during the last decades, there is still the necessity of understanding the impact of the HPV E6 and E7 oncogenes on host cells, ultimately leading to malignant transformation. Here, w...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00129-19
更新日期:2019-03-27 00:00:00
abstract::Human adenoviruses (HAdV), species D in particular (HAdV-D), are frequently associated with epidemic keratoconjunctivitis (EKC). Although the infection originates at the ocular surface epithelium, the mechanisms by which HAdV-Ds bypass the membrane-associated mucin (MAM)-rich glycocalyx of the ocular surface epitheliu...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00112-15
更新日期:2016-02-10 00:00:00
abstract::The rhoptry organelle is critical for the invasion of an erythrocyte by the malaria parasite Plasmodium falciparum. Despite their critical roles, the mechanisms behind their biogenesis are still poorly defined. Our earlier work had suggested that the interaction between the glycosylphosphatidylinositol (GPI)-anchored ...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00551-17
更新日期:2018-01-03 00:00:00
abstract::Increased knowledge about the role of horizontal gene transfer is key to improve our understanding of the spread of antimicrobial resistance (AMR) in human populations. We therefore studied the dissemination of the blaCTX-M-15 extended-spectrum-β-lactamase (ESBL) gene in Klebsiella pneumoniae isolates obtained from st...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00428-20
更新日期:2020-07-15 00:00:00
abstract::Spores, the infectious agents of many Firmicutes, are remarkably resilient cell forms. Even distant relatives can have similar spore architectures although some display unique features; they all incorporate protective proteinaceous envelopes. We previously found that Bacillus spores can achieve these protective proper...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00424-20
更新日期:2020-07-01 00:00:00
abstract::Increasing evidence shows that exosomes are key regulators in cancer cell-to-cell communication. Several reports on Epstein-Barr virus (EBV)-related malignancies demonstrate that latent membrane protein 1 (LMP1) secreted by exosomes derived from EBV- or LMP1-positive cells can promote cancer progression and metastasis...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00030-18
更新日期:2018-02-07 00:00:00
abstract::Nonribosomal peptide synthases produce short peptides in a manner that is distinct from classical mRNA-dependent ribosome-mediated translation. The Mycobacterium tuberculosis genome harbors a nonribosomal peptide synthase gene, nrp, which is part of a gene cluster proposed to be involved in the biosynthesis of isonitr...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00352-18
更新日期:2018-10-31 00:00:00
abstract::The gut microbiota has a key role in determining susceptibility to Clostridioides difficile infections (CDIs). However, much of the mechanistic work examining CDIs in mouse models uses animals obtained from a single source. We treated mice from 6 sources (2 University of Michigan colonies and 4 commercial vendors) wit...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00869-20
更新日期:2020-10-21 00:00:00
abstract::Candida albicans, a pervasive opportunistic pathogen, undergoes a unique phenotypic transition from a "white" phenotype to an "opaque" phenotype. The switch to opaque impacts gene expression, cell morphology, wall structure, metabolism, biofilm formation, mating, virulence, and colonization of the skin and gastrointes...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00918-20
更新日期:2020-09-23 00:00:00
abstract::Chikungunya virus (CHIKV) and Zika virus (ZIKV) emerged in the Americas in 2013. Limited antigenic variability of CHIKV and ZIKV may restrict urban transmission cycles due to population protective immunity. In Africa, sylvatic transmission cycles involving nonhuman primates (NHP) are known for CHIKV and ZIKV, causing ...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00523-17
更新日期:2018-01-31 00:00:00
abstract::Prebiotic oligosaccharides, such as fructooligosaccharides, are increasingly being used to modulate the composition and activity of the gut microbiota. However, carbohydrate utilization analyses and metagenomic studies recently revealed the ability of deleterious and uncultured human gut bacterial species to metaboliz...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00771-19
更新日期:2020-01-08 00:00:00
abstract::The fungal cell wall is a complex and dynamic entity essential for the development of fungi. It is composed mainly of polysaccharides that are synthetized by protein complexes. At the cell wall level, enzyme activities are involved in postsynthesis polysaccharide modifications such as cleavage, elongation, branching, ...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00397-19
更新日期:2019-07-31 00:00:00
abstract::In fungi, most metabolic processes are subject to regulation by light. Trichoderma reesei is adapted to degradation of plant cell walls and regulates production of the required enzymes in a manner dependent on the nutrient source and the light status. Here we investigated the interrelated relevance of two regulation l...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00089-17
更新日期:2017-05-10 00:00:00
abstract::Antibiotic resistance is a global crisis that threatens our ability to treat bacterial infections, such as tuberculosis, caused by Mycobacterium tuberculosis Of the 10 million cases of tuberculosis in 2017, approximately 19% of new cases and 43% of previously treated cases were caused by strains of M. tuberculosis res...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00606-19
更新日期:2019-09-11 00:00:00
abstract::The cell-to-cell heterogeneity in a bacterial population provides a rich response to environmental changes and robust survival of an isogenic population. Especially, the rare, extreme phenotypes can be important for survival under transient lethal conditions. We analyze the probability of having an extremely high or l...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00575-18
更新日期:2019-01-30 00:00:00
abstract::Competitive interactions between bacteria reveal physiological adaptations that benefit fitness. Bacillus subtilis is a Gram-positive species with several adaptive mechanisms for competition and environmental stress. Biofilm formation, sporulation, and motility are the outcomes of widespread changes in a population of...
journal_title:mSphere
pub_type: 杂志文章
doi:10.1128/mSphere.00586-17
更新日期:2018-02-21 00:00:00