| 1. |
- Moberg, Christina, et al.
(författare)
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De unga gör helt rätt när de stämmer staten
- 2022
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Ingår i: Aftonbladet. - 1103-9000.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
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| 2. |
- Kannan, K. K., et al.
(författare)
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Bror Erik Strandberg (1930-2018)
- 2018
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Ingår i: Acta Crystallographica Section D. - : International Union Of Crystallography. - 2059-7983. ; 74:7, s. 711-712
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Tidskriftsartikel (populärvet., debatt m.m.)
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| 3. |
- Liljas, Anders, et al.
(författare)
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Textbook of structural biology
- 2017. - 2
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Bok (refereegranskat)abstract
- This book provides a comprehensive coverage of the basic principles of structural biology, as well as an up-to-date summary of some main directions of research in the field. The relationship between structure and function is described in detail for soluble proteins, membrane proteins, membranes, and nucleic acids. There are several books covering protein structure and function, but none that give a complete picture, including nucleic acids, lipids, membranes and carbohydrates, all being of central importance in structural biology. The book covers state-of-the-art research in various areas. It is unique for its breadth of coverage by experts in the fields. The book is richly illustrated with more than 400 color figures to highlight the wide range of structures.
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| 4. |
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| 5. |
- Abdulkarim, Farhad, et al.
(författare)
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Mutations to kirromycin resistance occur in the interface of domains I and III of EF-Tu.GTP
- 1994
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Ingår i: FEBS Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 352, s. 118-122
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Tidskriftsartikel (refereegranskat)abstract
- The antibiotic kirromycin inhibits protein synthesis by binding to EF-Tu and preventing its release from the ribosome after GTP hydrolysis.We have isolated and sequenced a collection of kirromycin resistant tuf mutations and identified thirteen single amino acid substitutions at sevendifferent sites in EF-Tu. These have been mapped onto the 3D structures of EF-Tu’GTP and EF-Tu.GDP. In the active GTP form of EF-Tu themutations cluster on each side of the interface between domains I and III. We propose that this domain interface is the binding site for kirromycin.
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| 6. |
- Brandis, Gerrit, 1985-, et al.
(författare)
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Fitness-compensatory mutations in rifampicin-resistant RNA polymerase
- 2012
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Ingår i: Molecular Microbiology. - : Blackwell Publishing. - 0950-382X .- 1365-2958. ; 85:1, s. 142-151
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in rpoB (RNA polymerase β-subunit) can cause high-level resistance to rifampicin, an important first-line drug against tuberculosis. Most rifampicin-resistant (RifR) mutants selected in vitro have reduced fitness, and resistant clinical isolates of M. tuberculosis frequently carry multiple mutations in RNA polymerase genes. This supports a role for compensatory evolution in global epidemics of drug-resistant tuberculosis but the significance of secondary mutations outside rpoB has not been demonstrated or quantified. Using Salmonella as a model organism, and a previously characterized RifR mutation (rpoB R529C) as a starting point, independent lineages were evolved with selection for improved growth in the presence and absence of rifampicin. Compensatory mutations were identified in every lineage and were distributed between rpoA, rpoB and rpoC. Resistance was maintained in all strains showing that increased fitness by compensatory mutation was more likely than reversion. Genetic reconstructions demonstrated that the secondary mutations were responsible for increasing growth rate. Many of the compensatory mutations in rpoA and rpoC individually caused small but significant reductions in susceptibility to rifampicin, and some compensatory mutations in rpoB individually caused high-level resistance. These findings show that mutations in different components of RNA polymerase are responsible for fitness compensation of a RifR mutant.
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| 7. |
- Chapman, M. S., et al.
(författare)
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Structural Folds of Viral Proteins
- 2003
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Ingår i: Advances in Protein Chemistry. - 0065-3233 .- 1557-8941. ; 64, s. 125-196
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Tidskriftsartikel (populärvet., debatt m.m.)
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| 8. |
- Gan, Lu, et al.
(författare)
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Capsid Conformational Sampling in HK97 Maturation Visualized by X-Ray Crystallography and Cryo-EM
- 2006
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Ingår i: Structure. - : Elsevier BV. - 0969-2126 .- 1878-4186. ; 14:11, s. 1655-1665
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Tidskriftsartikel (refereegranskat)abstract
- Maturation of the bacteriophage HK97 capsid from a precursor (Prohead II) to the mature state (Head II) involves a 60 angstrom radial expansion. The mature particle is formed by 420 copies of the major capsid protein organized on a T = 7 laevo, lattice with each subunit covalently crosslinked to two neighbors. Well-characterized pH 4 expansion intermediates make HK97 valuable for investigating quaternary structural dynamics. Here, we use X-ray crystallography and cryo-EM to demonstrate that in the final transition in maturation (requiring neutral pH), pentons in Expansion Intermediate IV (EI-IV) reversibly sample 14 angstrom translations and 6 degrees rotations relative to a fixed hexon lattice. The limit of this trajectory corresponds to the Head II conformation that is secured at this extent only by the formation of the final class of covalent crosslinks. Mutants that cannot crosslink or EI-IV particles that have been rendered incapable of forming the final crosslink remain in the EI-IV state.
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| 9. |
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| 10. |
- Hammarlöf, Disa L., et al.
(författare)
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Temperature-sensitive mutants of RNase E in Salmonella enterica
- 2011
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Ingår i: Journal of Bacteriology. - 0021-9193 .- 1098-5530. ; 193:23, s. 6639-6650
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Tidskriftsartikel (refereegranskat)abstract
- RNase E has an important role in mRNA turnover and stable RNA processing although the reason for its essentiality is unknown. We isolated conditional mutants of RNase E to provide genetic tools to probe its essential function. In Salmonella enterica serovar Typhimurium an extreme slow-growth phenotype caused by mutant EF-Tu (Gln125Arg, tufA499) can be rescued by mutants of RNase E that have reduced activity. We exploited this phenotype to select mutations in RNase E and screened these for temperature sensitivity (ts) for growth. Four different ts mutations were identified, all in the N-terminal domain of RNase E: Gly66→Cys; Ile207→Ser; Ile207→Asn; Ala327→Pro. We also selected second-site mutations in RNase E that reversed temperature-sensitivity. The complete set of RNase E mutations (53 primary mutations including the ts mutations, and 23 double mutations) were analyzed for their possible effects on the structure and function of RNase E using the available 3-D structures. Most single mutations were predicted to destabilize the structure while second-site mutations that reversed the ts phenotype were predicted to restore stability to the structure. Three isogenic strain pairs carrying single or double mutations in RNase E (ts, and ts plus second-site mutation) were tested for their effects on the degradation, accumulation and processing of mRNA, rRNA and tRNA. The greatest defect was observed on rne mRNA autoregulation and this correlated with ability to rescue the tufA499-associated slow growth phenotype. This is consistent with the RNase E mutants being defective in initial binding or subsequent cleavage of an mRNA critical for fast growth.
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| 11. |
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| 12. |
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| 13. |
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| 14. |
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| 15. |
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| 16. |
- Larsson, Daniel, et al.
(författare)
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Virus Capsid Dissolution Studied by Microsecond Molecular Dynamics Simulations
- 2012
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Ingår i: PloS Computational Biology. - : Public Library of Science (PLoS). - 1553-734X .- 1553-7358. ; 8:5, s. e1002502-
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Tidskriftsartikel (refereegranskat)abstract
- Dissolution of many plant viruses is thought to start with swelling of the capsid caused by calcium removal following infection, but no high-resolution structures of swollen capsids exist. Here we have used microsecond all-atom molecular simulations to describe the dynamics of the capsid of satellite tobacco necrosis virus with and without the 92 structural calcium ions. The capsid expanded 2.5% upon removal of the calcium, in good agreement with experimental estimates. The water permeability of the native capsid was similar to that of a phospholipid membrane, but the permeability increased 10-fold after removing the calcium, predominantly between the 2-fold and 3-fold related subunits. The two calcium binding sites close to the icosahedral 3-fold symmetry axis were pivotal in the expansion and capsid-opening process, while the binding site on the 5-fold axis changed little structurally. These findings suggest that the dissociation of the capsid is initiated at the 3-fold axis.
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| 17. |
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| 18. |
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| 19. |
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| 20. |
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| 21. |
- Liljas, Lars
(författare)
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Virus assembly.
- 1999
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Ingår i: Curr Opin Struct Biol. - 0959-440X. ; 9:1, s. 129-34
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 22. |
- Nasertorabi, Fariborz, 1966-
(författare)
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Biochemical and Structural Studies on the Adaptor Protein p130Cas
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Crk associated substrate (Cas) is an adaptor protein that becomes phosphorylated upon integrin signaling and influences regulation of cell processes such as migration, proliferation and survival. It consists of multiple domains and regions that can interact with several signaling proteins involved in different signaling pathways. Cas was first discovered as a highly phosphorylated protein in v-Src and v-Crk transformed cells, showing involvement of this protein in cell transformation High level of Breast cancer antiestrogen resistance protein (BCAR-1), a homologue to Cas has shown to correlate with rapid reoccurrence of breast cancer and also create resistance towards Tamoxifen, the widely used medicine for receptor positive breast cancer patients. We have defined boundaries of two regions of Cas termed serine rich region (SRR) and Src binding domain (SBD) respectively and have isolated these segments for biochemical and structural studies. The structure of the serine rich part of Cas has been determined by NMR spectroscopy and reveals a four-helix bundle with unusually long loops. The 14-3-3 protein binds to Cas in a phospho-serine dependent manner and our study suggests that the binding site is located between two helices. The SH2-SH3 domain of a Src family kinase, Lck has also been crystallized in complex with a nine residue long peptide corresponding to the region in Cas that binds to SH2 domains. The structure of this complex has been solved at 2.7Å and shows that Cas binds Src family kinases (SFK) with high affinity suggesting a specific interaction between these two molecules. The biochemical studies on the specific binding site of these molecules show that SFK can bind to any of the phosphorylated tyrosines on the SH2 binding domain of Cas and only one phospho-tyrosine is enough to establish the binding. This binding assay does also indicate that SH3 binding domain of Cas is not essential for SFK binding.
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| 23. |
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| 24. |
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| 25. |
- Persson, Magnus, et al.
(författare)
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Prr1 Coat Protein Binding to its Translational Operator
- 2013
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Ingår i: Acta Crystallographica Section D. - 0907-4449 .- 1399-0047. ; 69, s. 367-372
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Tidskriftsartikel (refereegranskat)abstract
- In small RNA bacteriophages, the genomic RNA binds to the coat proteins when the viral capsid assembles. This is achieved through sequence-specific interactions between a coat-protein dimer and an RNA stem-loop that includes the start codon for the replicase gene. The structure of virus-like particles of the small RNA phage PRR1 bound to an RNAsegment corresponding to this stem-loop has been solved and the binding was compared with the related, and better investigated, phage MS2. The overall conformation of the RNA is found to be similar and the residues that are involved in RNA binding in PRR1 are the same as in MS2. The arrangement of the nucleotide bases in the loop of the stem-loop is different, leading to a difference in the stacking at the conserved Tyr86, which is equivalent to Tyr85 in MS2.
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| 26. |
- Persson, Magnus
(författare)
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Structural Studies of Bacteriophage PRR1 and HIV-1 protease
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Viruses are a diverse genera of organisms adapted to thrive in many different hosts from prokaryotic to eukaryotic.We present here the structure of bacteriophage PRR1 virus-like particle (VLP), belonging to Leviviridae family. Our structure reveals calcium ions in the VLP. Metal ions are rare in the VLP among the Leviviridae and the calcium ions were found to affect VLP stability. Gene expression in Leviviridae is controlled by a specific interaction between the viral coat protein that assembles to create the VLP, and the genomic RNA. This interaction has been thoroughly studied for the levivirus MS2 but other structural data are scarce. We have solved the structure of PRR1 VLP in complex with its RNA operator stem-loop. Binding of the stem-loop in PRR1 shows similarities to MS2 but also a different arrangement of the nucleotides, in the area of the loop that we could interpret, compared to MS2. The structures of PRR1 increase our knowledge about translational control in Leviviridae and add new information about particle stability within this family.The other virus we investigated is the more infamous human pathogen, the HIV. Because of the high mutation rate of HIV new drugs are needed on a continuous basis. We describe here the structure of two new protease inhibitors bound to the HIV-1 protease and compare them with two previously published inhibitors. Due to an extended P1´site the new compounds are able to exploit a new interaction to Phe53 in the protease structure.
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| 27. |
- Persson, Magnus, et al.
(författare)
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The capsid of the small RNA phage PRR1 is stabilized by metal ions.
- 2008
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Ingår i: Journal of molecular biology. - : Elsevier BV. - 1089-8638 .- 0022-2836. ; 383:4, s. 914-22
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Tidskriftsartikel (refereegranskat)abstract
- Many nonenveloped virus particles are stabilized by calcium ions bound in the interfaces between the protein subunits. These ions may have a role in the disassembly process. The small RNA phages of the Leviviridae family have T=3 quasi-symmetry and are unique among simple viruses in that they have a coat protein with a translational repressor activity and a fold that has not been observed in other viruses. The crystal structure of phage PRR1 has been determined to 3.5 A resolution. The structure shows a tentative binding site for a calcium ion close to the quasi-3-fold axis. The RNA-binding surface used for repressor activity is mostly conserved. The structure does not show any significant differences between quasi-equivalent subunits, which suggests that the assembly is not controlled by conformational switches as in many other simple viruses.
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| 28. |
- Plevka, Pavel, 1979-, et al.
(författare)
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Crystal packing of a bacteriophage MS2 coat protein mutant corresponds to octahedral particles
- 2008
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Ingår i: Protein Science. - : Wiley. - 0961-8368 .- 1469-896X. ; 17:10, s. 1731-1739
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Tidskriftsartikel (refereegranskat)abstract
- A covalent dimer of the bacteriophage MS2 coat protein was created by performing genetic fusion of two copies of the gene while removing the stop codon of the first gene. The dimer was crystallized in the cubic F432 space group. The organization of the asymmetric unit together with the F432 symmetry results in an arrangement of subunits that corresponds to T = 3 octahedral particles. The octahedral particles are probably artifacts created by the particular crystal packing. When it is not crystallized in the F cubic crystal form, the coat protein dimer appears to assemble into T = 3 icosahedral particles indistinguishable from the wild-type particles. To form an octahedral particle with closed surface, the dimer subunits interact at sharper angles than in the icosahedral arrangement. The fold of the covalent dimer is almost identical to the wild-type dimer with differences located in loops and in the covalent linker region. The main differences in the subunit packing between the octahedral and icosahedral arrangements are located close to the fourfold and fivefold symmetry axes where different sets of loops mediate the contacts. The volume of the wild-type virions is 7 times bigger than that of the octahedral particles.
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| 29. |
- Plevka, Pavel, 1979-, et al.
(författare)
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Structure and stability of icosahedral particles of a covalent coat protein dimer of bacteriophage MS2
- 2009
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Ingår i: Protein Science. - : Wiley. - 0961-8368 .- 1469-896X. ; 18:8, s. 1653-1661
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Tidskriftsartikel (refereegranskat)abstract
- Particles formed by the bacteriophage MS2 coat protein mutants with insertions in their surface loops induce a strong immune response against the inserted epitopes. The covalent dimers created by fusion of two copies of the coat protein gene are more tolerant to various insertions into the surface loops than the single subunits. We determined a 4.7Å-resolution crystal structure of an icosahedral particle assembled from covalent dimers and compared its stability to wildtype virions. The structure resembled the wildtype virion except for the intersubunit linker regions. The covalent dimer orientation was random with respect to both icosahedral twofold and quasi-twofold symmetry axes. A fraction of the particles was unstable in phosphate buffer because of assembly defects. Our results provide a structural background for design of modified covalent coat-protein dimer subunits for use in immunization.
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| 30. |
- Plevka, Pavel, 1979-
(författare)
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Structure of Small Icosahedral Viruses
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis presents structural studies on the plant virus Ryegrass mottle virus (RGMoV), the bacteriophage φCb5, and the icosahedral particles and octahedral crystal assembly of a bacteriophage MS2 coat protein mutant. In contrast to other sobemoviruses, the RGMoV coat protein is missing several residues in two of the loop regions important for capsid assembly. The first loop contributes to contacts between subunits around the quasi-three fold symmetry axis. The altered contact interface results in tilting of the subunits towards the quasi-threefold axis. The assembly of the T=3 capsid of sobemoviruses is controlled by the N-termini of the C subunits. The second and smaller RGMoV loop does not interact with the N-terminus of the C subunit as do the corresponding loops of other sobemoviruses. The loss of interaction has been compensated for by additional interactions between the N-terminal arms of RGMoV C subunits. The bacteriophage MS2 belongs to the Leviviridae family of small RNA phages. Covalent dimers of the coat protein with insertions in the surface loops are known to be highly immunogenic epitope carriers. We crystallized the icosahedral particle assembled from covalent coat protein dimers in space group P213. At 4.7Å resolution the structure resembles the wildtype MS2 virion except for the intersubunit linker regions. The covalent dimer also crystallized in the cubic space group F432. The organization of the asymmetric unit in combination with the F432 symmetry results in an arrangement of subunits that corresponds to T=3 octahedral particles. Our crystal structure of the bacteriophage φCb5 capsid showed that it is stabilized by four calcium ions per icosahedral asymmetric unit. One ion is located between the quasi-threefold related subunits and is important for formation of a network of hydrogen bonds stabilizing the interface. The remaining calcium ions stabilized the contacts within the coat protein dimer. There was electron density of three putative RNA nucleotides per icosahedral asymmetric unit in the φCb5 structure. The nucleotides mediated contacts between two subunits forming a dimer and a third subunit in another dimer. On the basis of these findings, we have proposed a model for φCb5 capsid assembly in which addition of coat protein dimers to the forming capsid is facilitated by interaction with the RNA genome. The structure of RGMoV increases our understanding of mechanisms controlling sobemovirus assembly. This knowledge could be used to create genetically modified plants resistant to sobemovirus infection. The modified capsids of leviviruses can be used in immunization and as vehicles for gene or therapeutic compound delivery.
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| 31. |
- Plevka, Pavel, 1979-, et al.
(författare)
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The Structure of Bacteriophage phi Cb5 Reveals a Role of the RNA Genome and Metal Ions in Particle Stability and Assembly
- 2009
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Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836 .- 1089-8638. ; 391:3, s. 635-647
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Tidskriftsartikel (refereegranskat)abstract
- The structure of the Leviviridae bacteriophage φCb5 virus-like particle has been determined at 2.9Å resolution and the structure of the native bacteriophage φCb5 at 3.6Å. The structures of the coat protein shell appear identical while differences are found in the organization of the density corresponding to the RNA. The capsid is built of coat protein dimers and in shape corresponds to a truncated icosahedron with T=3 quasi-symmetry. The capsid is stabilized by four calcium ions per icosahedral asymmetric unit. One is located at the symmetry axis relating the quasi-threefold related subunits and is part of an elaborate network of hydrogen bonds stabilizing the interface. The remaining calcium ions stabilize the contacts within the coat protein dimer. The stability of the φCb5 particles decreases when calcium ions are chelated with EDTA. In contrast to other leviviruses, φCb5 particles are destabilized in solutions with elevated salt concentrations. The model of the φCb5 capsid provides an explanation of the salt-induced destabilization of φCb5 since hydrogen bonds, salt bridges and calcium ions have important role in the intersubunit interactions. Electron density of three putative RNA nucleotides per icosahedral asymmetric unit has been observed in the φCb5 structure. The nucleotides mediate contacts between the two subunits forming a dimer and a third subunit in another dimer. We suggest a model for φCb5 capsid assembly in which addition of coat protein dimers to the forming capsid is facilitated by interaction with the RNA genome. The φCb5 structure is the first example in the levivirus family that provides insight into the mechanism by which the genome - coat protein interaction may accelerate the capsid assembly and increase capsid stability.
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| 32. |
- Plevka, Pavel, et al.
(författare)
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The three-dimensional structure of ryegrass mottle virus at 2.9 Å resolution
- 2007
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Ingår i: Virology. - : Elsevier BV. - 0042-6822 .- 1096-0341. ; 369:2, s. 364-374
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Tidskriftsartikel (refereegranskat)abstract
- The crystal structure of the sobemovirus Ryegrass mottle virus (RGMoV) has been determined at 2.9 Å resolution. The coat protein has a canonical jellyroll β-sandwich fold. In comparison to other sobemoviruses the RGMoV coat protein is missing several residues in two of the loop regions. The first loop contributes to contacts between subunits around the quasi-threefold symmetry axis. The altered contact interface results in tilting of the subunits towards the quasi-threefold axis. The assembly of the T = 3 capsid of sobemoviruses is controlled by the N-termini of C subunits forming a so-called β-annulus. The other loop that is smaller in the RGMoV structure contains a helix that participates in stabilization of the β-annulus in other sobemoviruses. The loss of interaction between the RGMoV loop and the β-annulus has been compensated for by additional interactions between the N-terminal arms. As a consequence of these differences, the diameter of the RGMoV particle is 8 Å smaller than that of the other sobemoviruses. The interactions of coat proteins in sobemovirus capsids involve calcium ions. Depletion of calcium ions results in particle swelling, which is considered a first step in disassembly. We could not identify any density for metal ions in the proximity of the conserved residues normally involved in calcium binding, but the RGMoV structure does not show any signs of swelling. A likely reason is the low pH (3.0) of the crystallization buffer in which the groups interacting with the calcium ions are not charged.
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| 33. |
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