GalaxyWEB server for protein structure prediction and refinement

Ko, Junsu; Park, Hahnbeom; Heo, Lim; Seok, Chaok

doi:10.1093/nar/gks493

Cited by 724 publications

(455 citation statements)

References 20 publications

Supporting

Mentioning

448

Contrasting

Unclassified

Order By: Relevance

“…The structural model of the HPV11 E1 helicase domain (aa 353 to 623) was generated using the I-TASSER suite (29) and refined with ModRefiner (30). The resulting model was submitted to the GalaxyWeb server (31) to predict the structure of the HPV11 E1 HD in its hexameric form using the GalaxyGemini program or, alternatively, to predict its structure in complex with the HPV11 E2 transactivation domain (TAD) (Protein Data Bank [PDB] 1R6K) using the Galaxy Refine Complex algorithm (29). A representation of the HPV11 E1 AR and C-tail in their extended conformation was obtained using the IntFOLD Server (32).…”

Section: Methodsmentioning

confidence: 99%

Requirement for the E1 Helicase C-Terminal Domain in Papillomavirus DNA Replication In Vivo

Bergvall

Gagnon

Titolo

et al. 2016

J Virol

View full text Add to dashboard Cite

The papillomavirus (PV) E1 helicase contains a conserved C-terminal domain (CTD), located next to its ATP-binding site, whose function in vivo is still poorly understood. The CTD is comprised of an alpha helix followed by an acidic region (AR) and a C-terminal extension termed the C-tail. Recent biochemical studies on bovine papillomavirus 1 (BPV1) E1 showed that the AR and C-tail regulate the oligomerization of the protein into a double hexamer at the origin. In this study, we assessed the importance of the CTD of human papillomavirus 11 (HPV11) E1 in vivo, using a cell-based DNA replication assay. Our results indicate that combined deletion of the AR and C-tail drastically reduces DNA replication, by 85%, and that further truncation into the alpha-helical region compromises the structural integrity of the E1 helicase domain and its interaction with E2. Surprisingly, removal of the C-tail alone or mutation of highly conserved residues within the domain still allows significant levels of DNA replication (55%). This is in contrast to the absolute requirement for the C-tail reported for BPV1 E1 in vitro and confirmed here in vivo. Characterization of chimeric proteins in which the AR and C-tail from HPV11 E1 were replaced by those of BPV1 indicated that while the function of the AR is transferable, that of the C-tail is not. Collectively, these findings define the contribution of the three CTD subdomains to the DNA replication activity of E1 in vivo and suggest that the function of the C-tail has evolved in a PV type-specific manner. IMPORTANCEWhile much is known about hexameric DNA helicases from superfamily 3, the papillomavirus E1 helicase contains a unique C-terminal domain (CTD) adjacent to its ATP-binding site. We show here that this CTD is important for the DNA replication activity of HPV11 E1 in vivo and that it can be divided into three functional subdomains that roughly correspond to the three conserved regions of the CTD: an alpha helix, needed for the structural integrity of the helicase domain, followed by an acidic region (AR) and a C-terminal tail (C-tail) that have been shown to regulate the oligomerization of BPV1 E1 in vitro. Characterization of E1 chimeras revealed that, while the function of the AR could be transferred from BPV1 E1 to HPV11 E1, that of the C-tail could not. These results suggest that the E1 CTD performs multiple functions in DNA replication, some of them in a virus type-specific manner.H uman papillomaviruses (HPVs) are small viruses with double-stranded DNA (dsDNA) genomes that infect both outer and mucosal stratified epithelium (for a recent review see reference 1). Of the more than 180 HPV genotypes described to date, about 20% infect the anogenital tract, causing either benign or precancerous lesions (2). In addition to their well-established role in inducing cervical and other anogenital cancers, HPVs have more recently been shown to be the causative agents for the majority of oropharyngeal cancers (3, 4).Only two HPV proteins, E1 and E2, are required for replicati...

show abstract

Section: Methodsmentioning

confidence: 99%

Requirement for the E1 Helicase C-Terminal Domain in Papillomavirus DNA Replication In Vivo

Bergvall

Gagnon

Titolo

et al. 2016

J Virol

View full text Add to dashboard Cite

show abstract

“…The tertiary structures of the P146, P179, P216 and P222, P179/N562P and P179/N562Y were predicted using Phyre2 server 30 . The results were refined using GalaxyWeb 31 . To evaluate the quality of the predicated 3D structures, Molprobity 32 was used and the best models were selected for further analysis.…”

Section: Sds-polyacrylamide Gel Electrophoresis Andmentioning

confidence: 99%

Dimerization: A structural feature for the protection of Hepatitis E virus capsid protein against trypsinization

Wei¹,

Meng²,

Behloul³

et al. 2018

Journal of Hepatology

View full text Add to dashboard Cite

“…The Fv (VH:VL) of huPT9 was obtained in GalaxyWeb [21]. A total of seven structures of human Fv (PDB ID: 3IU4, 3U6R, 1KXV, 2VYR, 2EAK, 3QYC, 3R0M) were used as templates to generate the homology model.…”

Section: Structure Modelingmentioning

confidence: 99%

Humanization of a phosphothreonine peptide-specific chicken antibody by combinatorial library optimization of the phosphoepitope-binding motif

Baek

Kim

2015

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

GalaxyWEB server for protein structure prediction and refinement

Cited by 724 publications

References 20 publications

Requirement for the E1 Helicase C-Terminal Domain in Papillomavirus DNA Replication In Vivo

Requirement for the E1 Helicase C-Terminal Domain in Papillomavirus DNA Replication In Vivo

Dimerization: A structural feature for the protection of Hepatitis E virus capsid protein against trypsinization

Humanization of a phosphothreonine peptide-specific chicken antibody by combinatorial library optimization of the phosphoepitope-binding motif

Contact Info

Product

Resources

About