Evidence map›Paper›PMID 17267502›Full record

ArticleJournal of virology2007

Structures of a human papillomavirus (HPV) E6 polypeptide bound to MAGUK proteins: mechanisms of targeting tumor suppressors by a high-risk HPV oncoprotein.

Yi Zhang, Jhimli Dasgupta, Runlin Z Ma, Lawrence Banks, Miranda Thomas, Xiaojiang S Chen

Abstract read
In one paragraph

Article in Journal of virology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed
3.8field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

64 citing papers in PubMed, 120 citations in OpenAlex.

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4 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 3 countries.

Yi ZhangMolecular and Computational Biology, University of Southern California, 1050 Childs Way, MCB201, Los Angeles, CA 90089, USA.
Jhimli Dasgupta
Runlin Z Ma
Lawrence Banks
Miranda Thomas
Xiaojiang S Chen
University of Southern California · USInternational Centre for Genetic Engineering and Biotechnology · ITInstitute of Genetics and Developmental Biology · CN

Funding

STRUCTURAL STUDIES OF PAPILLOMA VIRUSESR01AI048747 · NIAID · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CHEN, XIAOJIANG S · 2001 to 2005
$1.7M
NIAID NIH HHS R01 AI 048747NIAID NIH HHS R01 AI048747
6 · The paper itself

Abstract

Human papillomavirus (HPV) E6 oncoprotein targets certain tumor suppressors such as MAGI-1 and SAP97/hDlg for degradation. A short peptide at the C terminus of E6 interacts specifically with the PDZ domains of these tumor suppressors, which is a property unique to high-risk HPVs that are associated with cervical cancer. The detailed recognition mechanisms between HPV E6 and PDZ proteins are unclear. To understand the specific binding of cellular PDZ substrates by HPV E6, we have solved the crystal structures of the complexes containing a peptide from HPV18 E6 bound to three PDZ domains from MAGI-1 and SAP97/Dlg. The complex crystal structures reveal novel features of PDZ peptide recognition that explain why high-risk HPV E6 can specifically target these cellular tumor suppressors for destruction. Moreover, a new peptide-binding loop on these PDZs is identified as interacting with the E6 peptide. Furthermore, we have identified an arginine residue, unique to high-risk HPV E6 but outside the canonical core PDZ recognition motif, that plays an important role in the binding of the PDZs of both MAGI-I and SAP97/Dlg, the mutation of which abolishes E6's ability to degrade the two proteins. Finally, we have identified a dimer form of MAGI-1 PDZ domain 1 in the cocrystal structure with E6 peptide, which may have functional relevance for MAGI-1 activity. In addition to its novel insights into the biochemistry of PDZ interactions, this study is important for understanding HPV-induced oncogenesis; this could provide a basis for developing antiviral and anticancer compounds.

Indexed as

Adaptor Proteins, Signal TransducingAmino Acid MotifsConserved SequenceCrystallography, X-RayDimerizationDNA-Binding ProteinsGene DeletionModels, MolecularMolecular Sequence DataOncogene Proteins, ViralPeptide FragmentsProtein BindingProtein Structure, QuaternaryProtein Structure, TertiaryRepressor ProteinsSequence AlignmentAdaptor Proteins, Signal TransducingDNA-Binding ProteinsE6 protein, Human papillomavirus type 16E6 protein, Human papillomavirus type 18Oncogene Proteins, ViralPeptide FragmentsRepressor ProteinsTumor Suppressor Proteins

Identifiers

PMID17267502
PMCPMC1866053
OpenAlexW2101653819

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.