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dc.contributor.author
Karlsson, O. Andreas
dc.contributor.author
Ramirez, Juan
dc.contributor.author
Öberg, Daniel
dc.contributor.author
Malmqvist, Tony
dc.contributor.author
Engström, Åke
dc.contributor.author
Friberg, Maria
dc.contributor.author
Chi, Celestine N.
dc.contributor.author
Widersten, Mikael
dc.contributor.author
Travé, Gilles
dc.contributor.author
Nilsson, Mikael T.I.
dc.contributor.author
Jemth, Per
dc.date.accessioned
2018-10-25T14:39:17Z
dc.date.available
2017-06-12T18:07:13Z
dc.date.available
2018-10-24T09:27:55Z
dc.date.available
2018-10-25T14:39:17Z
dc.date.issued
2015-03-23
dc.identifier.other
10.1038/srep09382
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/125491
dc.identifier.doi
10.3929/ethz-b-000125491
dc.description.abstract
Chronic infection by high risk human papillomavirus (HPV) strains may lead to cancer. Expression of the two viral oncoproteins E6 and E7 is largely responsible for immortalization of infected cells. The HPV E6 is a small (approximately 150 residues) two domain protein that interacts with a number of cellular proteins including the ubiquitin ligase E6-associated protein (E6AP) and several PDZ-domain containing proteins. Our aim was to design a high-affinity binder for HPV E6 by linking two of its cellular targets. First, we improved the affinity of the second PDZ domain from SAP97 for the C-terminus of HPV E6 from the high-risk strain HPV18 using phage display. Second, we added a helix from E6AP to the N-terminus of the optimized PDZ variant, creating a chimeric bivalent binder, denoted PDZbody. Full-length HPV E6 proteins are difficult to express and purify. Nevertheless, we could measure the affinity of the PDZbody for E6 from another high-risk strain, HPV16 (Kd = 65 nM). Finally, the PDZbody was used to co-immunoprecipitate E6 protein from HPV18-immortalized HeLa cells, confirming the interaction between PDZbody and HPV18 E6 in a cellular context.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Nature Publishing Group
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
Protein design
en_US
dc.subject
Viral proteins
en_US
dc.title
Design of a PDZbody, a bivalent binder of the E6 protein from human papillomavirus.
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
ethz.journal.title
Scientific Reports
ethz.journal.volume
5
en_US
ethz.pages.start
9382
en_US
ethz.size
7 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.nebis
006751867
ethz.publication.place
London
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02515 - Laboratorium für Physikalische Chemie / Laboratory of Physical Chemistry::03782 - Riek, Roland / Riek, Roland
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02515 - Laboratorium für Physikalische Chemie / Laboratory of Physical Chemistry::03782 - Riek, Roland / Riek, Roland
ethz.date.deposited
2017-06-12T18:07:23Z
ethz.source
ECIT
ethz.identifier.importid
imp593655110243771463
ethz.ecitpid
pub:188096
ethz.eth
no
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-20T13:37:56Z
ethz.rosetta.lastUpdated
2019-01-02T14:55:32Z
ethz.rosetta.exportRequired
true
ethz.rosetta.versionExported
true
ethz.COinS
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