Protein transduction into human cells by adenovirus dodecahedron using WW domains as universal adaptors

Garcel, Aude; Gout, Evelyne; Timmins, Joanna; Chroboczek, Jadwiga; Fender, Pascal

doi:10.1002/jgm.862

Cited by 35 publications

(39 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…2C), the N-terminal part of the CAV-2 penton base is also 15 amino acids shorter than that of hAdV-5. The currently unresolved Nterminal part of the penton base (amino acids 1 to 49) contains two highly conserved PPXY (where X is any residue) motifs implicated in interactions with host cell WW domain-containing ubiquitin ligases (21,22). In the mature virion, this region is probably located under the penton base, where it interacts with other viral capsid proteins (20,45).…”

Section: Resultsmentioning

confidence: 99%

“…In the mature virion, this region is probably located under the penton base, where it interacts with other viral capsid proteins (20,45). The PPXY sequences are also present in CAV-2, suggesting that these sequences are critical for some phase in the AdV life cycle (22). The 15-amino-acid difference is too small to be interpreted in the EM map because it is in contact with other proteins on the inside of the virus capsid.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Three-Dimensional Structure of Canine Adenovirus Serotype 2 Capsid

Schoehn

Bakkouri

Fabry

et al. 2008

J Virol

View full text Add to dashboard Cite

There are more than 100 known adenovirus (AdV) serotypes, including 50 human serotypes. Because AdV-induced disease is relatively species specific, vectors derived from nonhuman serotypes may have wider clinical potential based, in part, on the lack of ubiquitous memory immunity. Whereas a few of the human serotype capsids have been studied at the structural level, none of the nonhuman serotypes has been analyzed. The basis laid by the analysis of human AdV (hAdV) has allowed us to determine and compare the threedimensional structure of the capsid of canine serotype 2 (CAV-2) to that of hAdV serotype 5 (hAdV-5). We show that CAV-2 capsid has a smoother structure than the human serotypes. Many of the external loops found in the hAdV-5 penton base and the hexon, against which the antibody response is directed, are shorter or absent in CAV-2. On the other hand, the CAV-2 fiber appears to be more complex, with two bends in the shaft. An interesting difference between the human and canine viruses is that the C-terminal part of protein IX is in a different position, making an antenna sticking out of the CAV-2 capsid. The comparison between the two viruses allows the identification of sites that should be easy to modify on the CAV-2 capsid for altering tissue tropism or other biological activities.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Three-Dimensional Structure of Canine Adenovirus Serotype 2 Capsid

Schoehn

Bakkouri

Fabry

et al. 2008

J Virol

View full text Add to dashboard Cite

show abstract

“…The assembly status of purified Dds was analyzed by native agarose gel electrophoresis. Protein samples were mixed with loading buffer (3 mM Tris-HCl, pH 8.0, containing 6 mM NH 4 Cl, 3 mM magnesium acetate, 14 mM potassium acetate, 10% glycerol and 0.005% bromophenol blue) and subjected to electrophoresis in 0.8% agarose gels containing 50 mM Tris and 200 mM glycine, pH 8 at 75 V at 4uC [51]. After electrophoresis proteins were stained with Coommassie Brilliant Blue (CBB) or blotted onto Immobilon-P transfer membrane in 20 mM Tris buffer pH 7.5, containing 150 mM NaCl and 2 mM EDTA.…”

Section: Protein Electrophoresis Antibodies and Immunological Analysesmentioning

confidence: 99%

“…HeLa cells (5610 4 ) were grown overnight on coverslips. Different amounts of Dd, Dd-BLM conjugate or free bleomycin were applied on cells in EMEM without serum.…”

Section: Confocal Microscopymentioning

confidence: 99%

Nanoporous Platforms for Cellular Sensing and Delivery

2011

Current Research in Pharmaceutical Technology

View full text Add to dashboard Cite

Background: Bleomycin (BLM) is an anticancer antibiotic used in many cancer regimens. Its utility is limited by systemic toxicity and dose-dependent pneumonitis able to progress to lung fibrosis. The latter can affect up to nearly 50% of the total patient population, out of which 3% will die. We propose to improve BLM delivery by tethering it to an efficient delivery vector. Adenovirus (Ad) dodecahedron base (DB) is a particulate vector composed of 12 copies of a pentameric viral protein responsible for virus penetration. The vector efficiently penetrates the plasma membrane, is liberated in the cytoplasm and has a propensity to concentrate around the nucleus; up to 300000 particles can be observed in one cell in vitro.

show abstract

“…Secondly, exogenous expression of WW1 domain of YAP2 has been shown to inhibit GAG-PPXY mediated budding of Rous sarcoma virus [58]. Moreover, a growing body of data suggest that the new adenovirus-based vectors with PPXY-containing dodecahedron proteins may provide an efficient system for delivering WW domains to cells at high efficiency [59, 60]. With these new tools at our disposal, it may also become feasible to deliver engineered WW domains to cancer cells so as to inhibit the YAP2-ErbB4 interaction.…”

Section: Discussionmentioning

confidence: 99%

Molecular basis of the binding of YAP transcriptional regulator to the ErbB4 receptor tyrosine kinase

et al. 2014

View full text Add to dashboard Cite

The newly discovered transactivation function of ErbB4 receptor tyrosine kinase is believed to be mediated by virtue of the ability of its proteolytically-cleaved intracellular domain (ICD) to physically associate with YAP2 transcriptional regulator. In an effort to unearth the molecular basis of YAP2-ErbB4 interaction, we have conducted a detailed biophysical analysis of the binding of WW domains of YAP2 to PPXY motifs located within the ICD of ErbB4. Our data show that the WW1 domain of YAP2 binds to PPXY motifs within the ICD in a differential manner and that this behavior is by and large replicated by the WW2 domain. Remarkably, while both WW domains absolutely require the integrity of the PPXY consensus sequence, non-consensus residues within and flanking this motif do not appear to be critical for binding. In spite of this shared mode of binding, the WW domains of YAP2 display distinct conformational dynamics in complex with PPXY motifs derived from ErbB4. Collectively, our study lends new insights into the molecular basis of a key protein-protein interaction involved in a diverse array of cellular processes.

show abstract

Protein transduction into human cells by adenovirus dodecahedron using WW domains as universal adaptors

Abstract: These data demonstrate the great potential of adenovirus dodecahedron in combination with WW domains as a protein transduction vector.

Cited by 35 publications

References 37 publications

Three-Dimensional Structure of Canine Adenovirus Serotype 2 Capsid

Three-Dimensional Structure of Canine Adenovirus Serotype 2 Capsid

Nanoporous Platforms for Cellular Sensing and Delivery

Molecular basis of the binding of YAP transcriptional regulator to the ErbB4 receptor tyrosine kinase

Contact Info

Product

Resources

About