scholarly journals Protein IX, a minor component of the human adenovirus capsid, is essential for the packaging of full length genomes.

1987 ◽  
Vol 6 (6) ◽  
pp. 1733-1739 ◽  
Author(s):  
G. Ghosh-Choudhury ◽  
Y. Haj-Ahmad ◽  
F. L. Graham
Keyword(s):  
Minor Component ◽  
Human Adenovirus ◽  
Full Length ◽  
Protein Ix ◽  
A Minor

scholarly journals Engineering of Adenovirus Vectors Containing Heterologous Peptide Sequences in the C Terminus of Capsid Protein IX

2002 ◽  
Vol 76 (14) ◽  
pp. 6893-6899 ◽  
Author(s):  
Igor P. Dmitriev ◽  
Elena A. Kashentseva ◽  
David T. Curiel
Keyword(s):  
Heparan Sulfate ◽  
Capsid Protein ◽  
Minor Component ◽  
Cell Types ◽  
Binding Motif ◽  
Flag Epitope ◽  
C Terminus ◽  
Protein Ix ◽  
A Minor ◽  
Carboxy Terminal

ABSTRACT The utility of the present generation of adenovirus (Ad) vectors for gene therapy applications could be improved by restricting native viral tropism to selected cell types. In order to achieve modification of Ad tropism, we proposed to exploit a minor component of viral capsid, protein IX (pIX), for genetic incorporation of targeting ligands. Based on the proposed structure of pIX, we hypothesized that its C terminus could be used as a site for incorporation of heterologous peptide sequences. We engineered recombinant Ad vectors containing modified pIX carrying a carboxy-terminal Flag epitope along with a heparan sulfate binding motif consisting of either eight consecutive lysines or a polylysine sequence. Using an anti-Flag antibody, we have shown that modified pIXs are incorporated into virions and display Flag-containing C-terminal sequences on the capsid surface. In addition, both lysine octapeptide and polylysine ligands were accessible for binding to heparin-coated beads. In contrast to virus bearing lysine octapeptide, Ad vector displaying a polylysine was capable of recognizing cellular heparan sulfate receptors. We have demonstrated that incorporation of a polylysine motif into the pIX ectodomain results in a significant augmentation of Ad fiber knob-independent infection of CAR-deficient cell types. Our data suggest that the pIX ectodomain can serve as an alternative to the fiber knob, penton base, and hexon proteins for incorporation of targeting ligands for the purpose of Ad tropism modification.

scholarly journals Fusion of Large Polypeptides to Human Adenovirus Type 5 Capsid Protein IX Can Compromise Virion Stability and DNA Packaging Capacity

2020 ◽  
Vol 94 (17) ◽  
Author(s):  
Kathy L. Poulin ◽  
Emily R. McFall ◽  
Grace Chan ◽  
Natacha B. Provost ◽  
Carin Christou ◽  
...  
Keyword(s):  
Capsid Protein ◽  
Fluorescent Proteins ◽  
Minor Component ◽  
Human Adenovirus ◽  
Heat Stability ◽  
Adenovirus Type ◽  
Dna Packaging ◽  
Wild Type ◽  
Packaging Capacity ◽  
Protein Ix

ABSTRACT The human adenovirus (HAdV) protein IX (pIX) is a minor component of the capsid that acts in part to stabilize the hexon-hexon interactions within the mature capsid. Virions lacking pIX have a reduced DNA packaging capacity and exhibit thermal instability. More recently, pIX has been developed as a platform for presentation of large polypeptides, such as fluorescent proteins or large targeting ligands, on the viral capsid. It is not known whether such modifications affect the natural ability of pIX to stabilize the HAdV virion. In this study, we show that addition of large polypeptides to pIX does not alter the natural stability of virions containing sub-wild-type-sized genomes. However, similar virions containing wild-type-sized genomes tend to genetically rearrange, likely due to selective pressure caused by virion instability as a result of compromised pIX function. IMPORTANCE Human adenovirus capsid protein IX (pIX) is involved in stabilizing the virion but has also been developed as a platform for presentation of various polypeptides on the surface of the virion. Whether such modifications affect the ability of pIX to stabilize the virion is unknown. We show that addition of large polypeptides to pIX can reduce both the DNA packaging capacity and the heat stability of the virion, which provides important guidance for the design of pIX-modified vectors.

scholarly journals Activation of Adenoviral Gene Expression by Protein IX Is Not Required for Efficient Virus Replication

2004 ◽  
Vol 78 (10) ◽  
pp. 5032-5037 ◽  
Author(s):  
Kathy L. Sargent ◽  
Robert A. Meulenbroek ◽  
Robin J. Parks
Keyword(s):  
Minor Component ◽  
Transient Transfection ◽  
Minimal Effect ◽  
Protein Coding ◽  
Coding Sequences ◽  
Late Genes ◽  
Viral Promoters ◽  
Protein Ix ◽  
A Minor

ABSTRACT The adenovirus (Ad) protein IX (pIX) is a minor component of the Ad capsid and is in part responsible for virion stability; virions lacking pIX are heat labile and lose their infectivity if the DNA content is greater than ∼35 kb. More recently, pIX has been identified as a transcriptional activator and, in transient-transfection assays, was shown to enhance expression from the E1A, E4, and major late Ad promoters by as much as 70-fold. In this study, we examined the role of pIX's ability to activate transcription during Ad replication. In transient-transfection assays, pIX had a minimal effect on expression from the E1A promoter, increasing expression by only 1.4-fold. We used helper-dependent Ad vectors, which had all Ad protein coding sequences deleted with the exception of E1A and which had capsids that either contained or lacked pIX, to show that pIX derived from decapsidation of the infecting virion does not influence expression of E1A. Similarly, expression of pIX from the Ad genome did not alter the expression levels of E1A. Viruses that had pIX deleted showed a threefold reduction in virus yield and expression of late genes compared to those of a similar virus which encoded pIX. This phenotype could not be rescued by growing the virus in cells which constitutively express pIX. Our results indicate that, although pIX can affect transcription from a variety of viral promoters, it does not appear to play a significant role in activation of Ad promoters during normal Ad replication.

scholarly journals Gentamicin B1 is not a minor gentamicin component with major nonsense mutation suppression activity

2018 ◽  
Author(s):  
Alireza Baradaran-Heravi ◽  
David E. Williams ◽  
David A. Powell ◽  
Aruna D. Balgi ◽  
Raymond J. Andersen ◽  
...  
Keyword(s):  
Nonsense Mutation ◽  
Genetic Diseases ◽  
Protein A ◽  
Minor Component ◽  
Premature Termination Codon ◽  
Full Length ◽  
Rare Genetic Diseases ◽  
Free Translation ◽  
High Concentrations ◽  
A Minor

AbstractNonsense mutations are single base substitutions that introduce a premature termination codon (PTC) preventing the formation of full-length protein. They are the causative mutations in about 10% of patients in a large number of rare genetic diseases. High concentrations of the antibiotic gentamicin can induce the incorporation of an amino acid at a PTC and formation of full-length protein, a process called PTC readthrough. Gentamicin is composed of several related aminoglycosides. We recently reported (doi/10.1073/pnas.1620982114) that the major gentamicin components that are responsible for its antibacterial activity showed weak to no PTC readthrough activity but that the minor component gentamicin B1 was a potent readthrough inducer. We have now determined that gentamicin B1 acquired from the sole supplier at the time the study was carried out was not gentamicin B1 but instead the closely related aminoglycoside G418. Gentamicin B1 recently became available from a second commercial source. Here, we provide nuclear magnetic resonance (NMR) assignment data for the two commercial compounds and verify only the second is indeed gentamicin B1. We show that gentamicin B1 lacks PTC readthrough activity in HDQ-P1 and DMS-114 cells homozygous for the TP53 R213X nonsense mutation, as well as in a cell-free translation assay.

Protonation effects on dynamic flux properties of aqueous metal complexes

2009 ◽  
Vol 74 (10) ◽  
pp. 1543-1557 ◽  
Author(s):  
Herman P. Van Leeuwen ◽  
Raewyn M. Town
Keyword(s):  
Complex Formation ◽  
Metal Ion ◽  
Good Description ◽  
Minor Component ◽  
Outer Sphere ◽  
Metal Species ◽  
Central Metal ◽  
Inner Sphere ◽  
A Minor ◽  
Protonated Ligand

The degree of (de)protonation of aqueous metal species has significant consequences for the kinetics of complex formation/dissociation. All protonated forms of both the ligand and the hydrated central metal ion contribute to the rate of complex formation to an extent weighted by the pertaining outer-sphere stabilities. Likewise, the lifetime of the uncomplexed metal is determined by all the various protonated ligand species. Therefore, the interfacial reaction layer thickness, μ, and the ensuing kinetic flux, Jkin, are more involved than in the conventional case. All inner-sphere complexes contribute to the overall rate of dissociation, as weighted by their respective rate constants for dissociation, kd. The presence of inner-sphere deprotonated H2O, or of outer-sphere protonated ligand, generally has a great impact on kd of the inner-sphere complex. Consequently, the overall flux can be dominated by a species that is a minor component of the bulk speciation. The concepts are shown to provide a good description of experimental stripping chronopotentiometric data for several protonated metal–ligand systems.

Petrography and provenance of the Marambio Group, Vega Island, Antarctica

1994 ◽  
Vol 6 (4) ◽  
pp. 517-527 ◽  
Author(s):  
Duncan Pirrie
Keyword(s):  
Late Cretaceous ◽  
Sedimentary Rocks ◽  
Clay Mineralogy ◽  
Minor Component ◽  
Source Area ◽  
Low Grade ◽  
Western Margin ◽  
Sediment Input ◽  
A Minor ◽  
Sandstone Petrography

Late Cretaceous sedimentary rocks assigned to the Santa Marta (Herbert Sound Member) and López de Bertodano (Cape Lamb and Sandwich Bluff members) formations of the Marambio Group, crop out on Cape Lamb, Vega Island. Although previous studies have recognized that these sedimentary rocks were derived from the northern Antarctic Peninsula region, the work presented here allows the provenance and palaeogeographical evolution of the region to be described in detail. On the basis of both sandstone petrography and clay mineralogy, the Herbert Sound and Cape Lamb members reflect sediment input from a low relief source area, with sand grade sediment sourced from low grade metasediments, and clay grade sediment ultimately derived from the weathering of an andesitic source area. In contrast, the Sandwich Bluff Member reflects a switch to a predominantly andesitic volcaniclastic source. However, this sediment was largely derived from older volcanic suites due to renewed source area uplift, with only a minor component from coeval volcanism. Regional uplift of both the arc terrane and the western margin of the James Ross Basin was likely during the Maastrichtian.

scholarly journals Species pattern of phosphatidylinositol from lung surfactant and a comparison of the species pattern of phosphatidylinositol and phosphatidylglycerol synthesized de novo in lung microsomal fractions

1988 ◽  
Vol 254 (1) ◽  
pp. 67-71 ◽  
Author(s):  
B Rüstow ◽  
Y Nakagawa ◽  
H Rabe ◽  
K Waku ◽  
D Kunze
Keyword(s):  
Lung Function ◽  
Molecular Species ◽  
De Novo ◽  
Lung Surfactant ◽  
Minor Component ◽  
Main Species ◽  
Surfactant Phospholipids ◽  
Species Pattern ◽  
A Minor

1. Phosphatidylinositol (PI) is a minor component of lung surfactant which may be able to replace the functionally important phosphatidylglycerol (PG) [Beppu, Clements & Goerke (1983) J. Appl. Physiol. 55, 496-502] without disturbing lung function. The dipalmitoyl species is one of the main species for both PI (14.4%) and PG (16.9%). Besides the C16:0--C16:0 species, the C16:0--C18:0, C16:0--C18:1, C16:0--C18:2 and C18:0--C18:1 species showed comparable proportions in the PG and PI fractions. These similarities of the species patterns and the acidic character of both phospholipids could explain why surfactant PG may be replaced by PI. 2. PI and PG were radiolabelled by incubation of microsomal fractions with [14C]glycerol 3-phosphate (Gro3P). For 11 out of 14 molecular species of PI and PG we measured comparable proportions of radioactivity. The radioactivity of these 11 species accounted together for more than 80% of the total. The addition of inositol to the incubation system decreased the incorporation in vitro of Gro3P into PG and CDP-DG (diacylglycerol) of lung microsomes (microsomal fractions), but did not change the distribution of radioactivity among the molecular species of PG. These results supported the idea that both acidic surfactant phospholipids may be synthesized de novo from a common CDP-DG pool in lung microsomes.

scholarly journals Recreational Harvest of Sharks and Rays in Western Australia Is Only a Minor Component of the Total Harvest

2021 ◽  
Vol 13 (11) ◽  
pp. 6215
Author(s):  
Matias Braccini ◽  
Eva Lai ◽  
Karina Ryan ◽  
Stephen Taylor
Keyword(s):  
Western Australia ◽  
Minor Component ◽  
The North ◽  
Commercial Harvest ◽  
Unknown Status ◽  
Reef Sharks ◽  
Conservation Concern ◽  
Taxonomic Groups ◽  
A Minor ◽  
Port Jackson

Sharks and rays are a global conservation concern with an increasing number of species considered at risk of extinction, mostly due to overfishing. Although the recreational harvest of sharks and rays is poorly documented and generally minimal, it can be comparable to the commercial harvest. In this study, we quantified the recreational harvest of sharks and rays in Western Australia, a region with a marine coastline greater than 20,000 km. A total of 33 species/taxonomic groups were identified, with the harvest dominated by dusky and bronze whalers, blacktip reef sharks, gummy sharks, Port Jackson sharks, wobbegongs, and rays and skates. Eighty-five percent of individuals were released with an unknown status (alive or dead). We found a latitudinal gradient of species composition, with tropical and subtropical species of the genus Carcharhinus dominating in the north and temperate species from a range of families dominating in the south. Overall, our findings showed that the recreational harvest was negligible when compared with commercial landings.

Sign in / Sign up

Export Citation Format

Share Document