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Order Bunyavirales
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
The 3D structure of the ectodomain of the PUUV Gc glycoprotein, expressed in inset Sf9 cells, was solved using x-ray crystallography at pH 6.0 and 8.0 to 1.8 Å and 2.3 Å resolutions, respectively, where both structures revealed a class II membrane fusion protein fold in its post-fusion trimeric conformation (Willensky et al. 2016).
Genetics and Biosynthesis of Lipopolysaccharide O-Antigens
Published in Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison, Endotoxin in Health and Disease, 2020
Wendy J. Keenleyside, Chris Whitfield
It is a conceivable and attractive hypothesis that electron microscopy identifies a scaffold-like translocation system exporting nascent LPS (or other) molecules to the cell surface. Although no LPS-specific translocation candidates have been identified, studies on group II capsule synthesis in E. coli may provide some insight into a possible mechanism. The model recently proposed for synthesis and export of the group II capsular polysaccharides (87) also implicates zones of adhesion in polysaccharide export. In this model, proteins encoded by the kps cluster (capsular polysaccharide biosynthesis) form a multicomponent synthetic/translocation complex consisting of the cytoplasmic transferases, the ABC transporter, plus (minimally) two periplasmic proteins and a porin. Interestingly, one of the periplasmic proteins, KpsE, shares similarities with membrane-fusion proteins (87). The other periplasmic protein, KpsD, is postulated to span the periplasm, where it recruits an outer membrane porin, as well as interacting with the nascent polysaccharide as it emerges from the ABC transporter. Given the flexibility of the E. coli K-12 system for translocating heterologous O-PSs, it seems unlikely that any “fusion” protein such as KpsE interacts specifically with the plasma membrane components of the O-PS synthetic complex.
Silver as an Antimicrobial Agent: The Resistance Issue
Published in Huiliang Cao, Silver Nanoparticles for Antibacterial Devices, 2017
Kristel Mijnendonckx, Rob Van Houdt
The silCFBA(orf105)PRSE gene products mediate silver resistance via active efflux and silver sequestration in the periplasm. SilF, a periplasmic chaperone protein, probably transports Ag+ to the SilCBA complex (Figure 7.2). This complex forms a three-polypeptide membrane potential-dependent cation/proton antiporter system that spans the entire cell membrane and belongs to the Heavy Metal Efflux-Resistance Nodulation cell Division (HME-RND) family of efflux. The complex consists of an efflux pump (SilA), an outer membrane factor (SilC) and a membrane fusion protein (SilB) and pumps Ag+ from the periplasm to the exterior of the cell (Franke 2007; Silver 2003). The orf105 gene, coding for a hypothetical protein of 105 aa, was recently reanalysed and was predicted to code for a periplasmic metal chaperone of 146 aa that contains the conserved metal-binding site CxxC and shares 45% protein identity with CopG from Cupriavidus metallidurans CH34 (Randall et al. 2015). SilP is a putative P-type ATPase efflux pump that transports silver ions from the cell cytoplasm to the periplasm (Franke 2007; Silver 2003). However, neither silP nor orf105 is essential for silver resistance as deletion mutants of silP or orf105 or both did not show an increased silver sensitivity (Randall et al. 2015). The transcription of the silCFBA(ORF105aa)P genes is controlled by the two-component regulatory system SilRS, consisting of a transmembrane histidine kinase SilS and a response regulator SilR. This regulatory system is homologous to other two-component regulatory systems involved in the regulation of metal resistance (Franke 2007; Silver 2003). Finally, the silE gene located downstream of silRS, is not controlled by SilRS; nevertheless, transcription is strongly induced in the presence of Ag+ (Silver et al. 1999). SilE codes for a periplasmic protein that shares 48% identity with PcoE, which acts as a ‘metal sponge’ because of its ability to bind multiple Cu+ and Ag+ ions and is encoded by the pcoABCDRSE copper resistance from E. coli plasmid pRJ1004 (Zimmermann et al. 2012). SilE could provide a first line of defense by binding Ag+ before it enters the cytoplasm, as one SilE molecule can bind up to 38 Ag+ ions depending on the experimental conditions (Silver et al. 1999). Additionally, it could act as a chaperone, transporting Ag+ ions to the SilCBA complex either directly or via SilF (Franke 2007; Randall et al. 2015; Silver 2003).
Recent trends in next generation immunoinformatics harnessed for universal coronavirus vaccine design
Published in Pathogens and Global Health, 2023
Chin Peng Lim, Boon Hui Kok, Hui Ting Lim, Candy Chuah, Badarulhisam Abdul Rahman, Abu Bakar Abdul Majeed, Michelle Wykes, Chiuan Herng Leow, Chiuan Yee Leow
S protein binds to one another naturally into a homo-trimer, resembling Class I membrane fusion protein [71]. S protein comprises two subunits. The S1 subunit is subdivided into N-terminal domain (NTD) and C-terminal domain (CTD). The RBD is located in the CTD. On the other hand, S2 subunit contains the basic elements responsible for membrane fusion, that are, fusion peptide (FP), heptad repeats (HR), membrane proximal external region (MPER) and transmembrane domain (TM). Full-length S protein, S1 subunit, RBD, NTD and FP have been investigated as potential targets of vaccines. The RBD is the most studied due to the fact that it attaches straight to the ACE2 receptor on the host cells. RBD immunization induced antibodies are capable of blocking this interaction and thus effectively minimize the infection [72]. To elaborate, the RBD is conserved relative to the S1 subunit, plus many neutralizing epitopes are found within this domain, making it an excellent candidate for inclusion in a vaccine [73]. N protein is located inside the virus, where it surrounds the viral RNA and forms a helical nucleocapsid. This protein, the most abundant protein in coronavirus, is relatively more conserved than S protein [74]. It is highly antigenic and suitable as a marker for diagnostic purposes [72]. Studies have stated that E protein is a noticeable virulence factor [75]. Along with S and E proteins, M proteins are also found on the viral envelope and are the major component needed for initiating viral-budding. M protein is abundant on the viral envelope (surface) and is well conserved among different species [76].
The development of efflux pump inhibitors to treat Gram-negative infections
Published in Expert Opinion on Drug Discovery, 2018
Paula Blanco, Fernando Sanz-García, Sara Hernando-Amado, José Luis Martínez, Manuel Alcalde-Rico
MDR efflux pumps can be grouped in five different structural families, namely Small Multidrug Resistance transporters, Multi And Toxic compound Extrusion efflux pumps, Major Facilitator Superfamily proteins, ATP Binding Cassette (ABC) transporters and the Resistance Nodulation and cell Division (RND) family of efflux pumps. While some of these transporters can work independently of any other protein, others form multiprotein complexes, which include the efflux pump itself, an outer membrane protein, and a membrane fusion protein. In the current article, we present updated information on the current situation concerning the search of EPIs and discuss how the development of these compounds may help in fighting the antibiotic resistance (and eventually the infectivity) displayed by Gram-negative bacterial pathogens. The review mainly focuses on RND efflux pumps, since these systems stand as main players in intrinsic and acquired resistance to antibiotics in Gram-negative organisms [13]. Consequently, most efforts in the development of adjuvants for treating Gram-negative bacterial infections have concentrated in the development of anti-RND EPIs.
Modified mixed nanomicelles with collagen peptides enhanced oral absorption of Cucurbitacin B: preparation and evaluation
Published in Drug Delivery, 2018
Lan Tang, Lulu Fu, Zhuanfeng Zhu, Yan Yang, Boxuan Sun, Weiguang Shan, Zhenhai Zhang
A considerable amount of research on topics such as liposomes, micelles, and solid lipid nanoparticles have been reported to improve drug solubility (Gao et al., 2012; Tapeinos et al., 2017; Zhang et al., 2017). Currently, the carrier that has been reported to potentially promote drug transport across the membrane mainly includes plant lectins, membrane fusion proteins, and cell-penetrating peptides (CPPs) (Mora et al., 2016; Zheng et al., 2016; Zhu et al., 2016). Among them, CPPs, a series of short peptides, were found to be supremely effective in enhancing penetration through biological membranes for different cargos, such as micelles, liposomes, and solid lipid nanoparticles (Jiang et al., 2012; Ramsey & Flynn, 2015). The CPPs were usually prepared by solid phase peptide synthesis or prokaryotic expression, the method which was considered complex and expensive.