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21.
22.
The structure of immature West Nile virus particles, propagated in the presence of ammonium chloride to block virus maturation in the low-pH environment of the trans-Golgi network, was determined by cryo-electron microscopy (cryo-EM). The structure of these particles was similar to that of immature West Nile virus particles found as a minor component of mature virus samples (naturally occurring immature particles [NOIPs]). The structures of mature infectious flaviviruses are radically different from those of the immature particles. The similarity of the ammonium chloride-treated particles and NOIPs suggests either that the NOIPs have not undergone any conformational change during maturation or that the conformational change is reversible. Comparison with the cryo-EM reconstruction of immature dengue virus established the locations of the N-linked glycosylation sites of these viruses, verifying the interpretation of the reconstructions of the immature flaviviruses. 相似文献
23.
Numerical simulation of saccular aneurysm hemodynamics: influence of morphology on rupture risk 总被引:1,自引:0,他引:1
The governing equations for pulsatile fluid flow were solved in their finite volume formulation in order to simulate blood flow in a variety of three-dimensional aneurysm geometries. The influence of geometric factors on flow patterns and fluid mechanical forces was studied with the goal of identifying the risk of aneurysm rupture. Aneurysm morphology was characterized by quantitative shape indices reflecting the three dimensionality of the vasculature derived from clinical studies. Recirculation zones and secondary flows were observed in aneurysms and arteries. Regions of extreme and alternating shear stress were observed and identified as sites for potential aneurysm rupture. The ellipticity of an aneurysm was observed to be strongly correlated with wall shear stress at the aneurysm fundus, while its non-sphericity, volume, and degree of undulation were more weakly correlated. 相似文献
24.
Florian M. Rossmann Isabelle Hug Matteo Sangermani Urs Jenal Morgan Beeby 《Molecular microbiology》2020,114(3):443-453
Bacterial flagellar motility is controlled by the binding of CheY proteins to the cytoplasmic switch complex of the flagellar motor, resulting in changes in swimming speed or direction. Despite its importance for motor function, structural information about the interaction between effector proteins and the motor are scarce. To address this gap in knowledge, we used electron cryotomography and subtomogram averaging to visualize such interactions inside Caulobacter crescentus cells. In C. crescentus, several CheY homologs regulate motor function for different aspects of the bacterial lifestyle. We used subtomogram averaging to image binding of the CheY family protein CleD to the cytoplasmic Cring switch complex, the control center of the flagellar motor. This unambiguously confirmed the orientation of the motor switch protein FliM and the binding of a member of the CheY protein family to the outside rim of the C ring. We also uncovered previously unknown structural elaborations of the alphaproteobacterial flagellar motor, including two novel periplasmic ring structures, and the stator ring harboring eleven stator units, adding to our growing catalog of bacterial flagellar diversity. 相似文献
25.
Xiao C Chipman PR Battisti AJ Bowman VD Renesto P Raoult D Rossmann MG 《Journal of molecular biology》2005,353(3):493-496
Mimivirus is the largest known virus. Using cryo-electron microscopy, the virus was shown to be icosahedral, covered by long fibers, and appears to have at least two lipid membranes within its protein capsid. A unique vertex, presumably for attachment and infection of the host, can be seen for particles that have a suitable orientation on the micrographs. 相似文献
26.
Fokine A Kostyuchenko VA Efimov AV Kurochkina LP Sykilinda NN Robben J Volckaert G Hoenger A Chipman PR Battisti AJ Rossmann MG Mesyanzhinov VV 《Journal of molecular biology》2005,352(1):117-124
The three-dimensional structure of the Pseudomonas aeruginosa bacteriophage phiKZ head has been determined by cryo-electron microscopy and image reconstruction to 18A resolution. The head has icosahedral symmetry measuring 1455 A in diameter along 5-fold axes and a unique portal vertex to which is attached an approximately 1800 A-long contractile tail. The 65 kDa major capsid protein, gp120, is organized into a surface lattice of hexamers, with T = 27 triangulation. The shape and size of the hexamers is similar to the hexameric building blocks of the bacteriophages T4, phi29, P22, and HK97. Pentameric vertices of the capsid are occupied by complexes composed of several special vertex proteins. The double-stranded genomic DNA is packaged into a highly condensed series of layers, separated by 24 A, that follow the contour of the inner wall of the capsid. 相似文献
27.
28.
Metals are vital for a huge number of physiological processes in the human body, but can also destroy health when the concentration is not within the physiologically favourable range. Cigarette smoking interferes with the carefully controlled metal homeostasis of the human body. This review focuses on the consequences of metal delivery to the human body by cigarette smoking and discusses the body's responses. The metal content of tobacco plants, smoke, the circulation, and various organs is discussed. Finally, we link individual cigarette smoke contained metals to the genesis of human diseases. 相似文献
29.
Nandhagopal N Simpson AA Johnson MC Francisco AB Schatz GW Rossmann MG Vogt VM 《Journal of molecular biology》2004,335(1):275-282
The structure of the N-terminal domain (NTD) of Rous sarcoma virus (RSV) capsid protein (CA), with an upstream 25 amino acid residue extension corresponding to the C-terminal portion of the Gag p10 protein, has been determined by X-ray crystallography. Purified Gag proteins of retroviruses can assemble in vitro into virus-like particles closely resembling in vivo-assembled immature virus particles, but without a membrane. When the 25 amino acid residues upstream of CA are deleted, Gag assembles into tubular particles. The same phenotype is observed in vivo. Thus, these residues act as a “shape determinant” promoting spherical assembly, when they are present, or tubular assembly, when they are absent. We show that, unlike the NTD on its own, the extended NTD protein has no β-hairpin loop at the N terminus of CA and that the molecule forms a dimer in which the amino-terminal extension forms the interface between monomers. Since dimerization of Gag has been inferred to be a critical step in assembly of spherical, immature Gag particles, the dimer interface may represent a structural feature that is essential in retrovirus assembly. 相似文献
30.
Ye Xiang Ulrich Baxa Ying Zhang Alasdair C. Steven Gentry L. Lewis James L. Van Etten Michael G. Rossmann 《Journal of virology》2010,84(23):12265-12273
The chloroviruses (family Phycodnaviridae), unlike most viruses, encode some, if not most, of the enzymes involved in the glycosylation of their structural proteins. Annotation of the gene product B736L from chlorovirus NY-2A suggests that it is a glycosyltransferase. The structure of the recombinantly expressed B736L protein was determined by X-ray crystallography to 2.3-Å resolution, and the protein was shown to have two nucleotide-binding folds like other glycosyltransferase type B enzymes. This is the second structure of a chlorovirus-encoded glycosyltransferase and the first structure of a chlorovirus type B enzyme to be determined. B736L is a retaining enzyme and belongs to glycosyltransferase family 4. The donor substrate was identified as GDP-mannose by isothermal titration calorimetry and was shown to bind into the cleft between the two domains in the protein. The active form of the enzyme is probably a dimer in which the active centers are separated by about 40 Å.Glycosyltransferases constitute a large family of enzymes that catalyze the transfer of sugar moieties from donor molecules to specific acceptor molecules. Unlike other enzyme families that usually share conserved features in their primary sequences, glycosyltransferases can have highly diversified sequences that have been grouped into more than 90 families (designated GTn, where n = 1, 2, …) (http://www.CAZy.org) (1, 15). However, two families, GT2 and GT4, account for about half of the total number of glycosyltransferases. Despite the large variation in the primary sequences of glycosyltransferases, their three-dimensional structures are usually conserved. There are two major glycosyltransferase structural types, named GT-A and GT-B. The GT-A members contain a single nucleotide-binding domain consisting of six parallel β-strands flanked by connecting α-helices (referred to as a “Rossmann fold” in most of the literature on these enzymes and herein). GT-A enzyme activities are usually metal ion dependent. The GT-B type glycosyltransferases have two Rossmann folds separated by a cleft that forms the substrate-binding site. Metal ions are normally not required for GT-B function. Based on their catalytic mechanism, glycosyltransferases are also classified as either retaining or inverting enzymes depending on the geometry between the sugar donor and the receptor in the product molecule (e.g., depending on whether the anomeric carbon atom is linked to the acceptor via its α or β position). If the anomeric carbon atom has the same configuration in the donor and in the product, the enzyme is classified as a retaining enzyme; if the configurations are different, the enzyme is considered to be an inverting enzyme (2).Many viruses, especially those that infect eukaryotic cells, have extensively glycosylated structural proteins. Glycans coating viral structural proteins serve multiple biological roles, e.g., they mimic host glycans to evade host cell immune reactions, aid in folding or assembly of viral structural proteins, function as a receptor recognized by cell surface proteins, or aid in stabilizing viral particles (see, e.g., reference 36).Typically, viruses use host-encoded glycosyltransferases and glycosidases located in the endoplasmic reticulum (ER) and Golgi apparatus to add and remove N-linked sugar residues from virus glycoproteins either during or shortly after translation of the protein. This posttranslational processing aids in protein folding and requires other host-encoded enzymes. After folding and assembly, virus glycoproteins are transported by host-sorting and membrane transport functions to virus-specified regions in host membranes, where they displace host glycoproteins. Progeny viruses then bud through these virus-specific target membranes, in what is usually the final step in the assembly of infectious virions (3, 14, 21, 36). Thus, nascent viruses become infectious only by budding through the target membrane, usually the plasma membrane, as they are released from the cell. Consequently, the glycan portion of virus glycoproteins is host specific. The theme that emerges is that virus glycoproteins are synthesized and glycosylated by the same mechanisms as host glycoproteins. Therefore, the only way to alter glycosylation of virus proteins is to either grow the virus in a different host or have a mutation in the virus protein that alters the protein glycosylation site.One explanation for this scenario is that, in general, viruses lack genes encoding glycosyltransferases. However, a few virus-encoded glycosyltransferases have been reported in recent years (see reference 17 for a review). Often these virus-encoded glycosyltransferases add sugars to compounds other than proteins. For instance, some phage-encoded glycosyltransferases modify virus DNA to protect it from host restriction endonucleases (see, e.g., reference 10), and a glycosyltransferase encoded by baculoviruses modifies a host insect ecdysteroid hormone, leading to its inactivation (22). Bovine herpesvirus 4 encodes a β-1,6-N-acetyl-glucosaminyltransferase that is localized in the Golgi apparatus and is probably involved in posttranslational modification of the virus structural proteins (32).One group of viruses differs from the scenario that viruses use the host machinery located in the ER and the Golgi apparatus to glycosylate their glycoproteins. These viruses are the large, plaque-forming, double-stranded DNA (dsDNA)-containing chloroviruses (family Phycodnaviridae) that infect eukaryotic algae (4, 34, 39, 40). The chloroviruses have up to 400 protein-encoding genes (or coding sequences [CDSs]). Annotation of six chlorovirus genomes showed that each virus encodes 3 to 6 putative glycosyltransferases (7-9, 16, 33). Three of these viruses, NY-2A, AR158, and the prototype chlorovirus Paramecium bursaria chlorella virus 1 (PBCV-1), infect Chlorella strain NC64A. Two of the viruses, MT325 and FR483, infect Chlorella Pbi, and one of them, Acanthocystis turfacea chlorella virus (ATCV-1), infects Chlorella SAG 3.83.Glycosylation of the PBCV-1 major capsid protein, Vp54, is at least partially performed by the viral glycosyltransferases (11, 20, 33, 38, 41). PBCV-1 encodes 5 putative glycosyltransferases. A previous structural study established that the N-terminal 211 amino acids of the A64R protein from PBCV-1 form a GT-A group glycosyltransferase that is a retaining enzyme belonging to the GT34 family and that UDP-glucose possibly serves as the donor sugar (41).Among the four additional PBCV-1 glycosyltransferase-encoding genes, gene a546l encodes a 396-amino-acid protein that resembles members in the GT4 family of glycosyltransferases, based on amino acid sequence comparison of members in the CAZy classification (1, 15). Homologs of this protein, A546L, are encoded by 3 other chloroviruses, NY-2A, AR158, and ATCV-1. Here, we report the crystal structure of one of these homologs, B736L, at 2.3-Å resolution. 相似文献