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  • Karlsson, O. AndreasUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi (author)

Design of a PDZbody, a bivalent binder of the E6 protein from human papillomavirus

  • Article/chapterEnglish2015

Publisher, publication year, extent ...

  • 2015-03-23
  • Springer Science and Business Media LLC,2015
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-258849
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-258849URI
  • https://doi.org/10.1038/srep09382DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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 (K-d = 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.

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Added entries (persons, corporate bodies, meetings, titles ...)

  • Ramirez, Juan (author)
  • Öberg, DanielUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi(Swepub:uu)daobe475 (author)
  • Malmqvist, TonyUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi (author)
  • Engström, ÅkeUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi(Swepub:uu)akeengs (author)
  • Friberg, MariaUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi (author)
  • Chi, Celestine N.Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi(Swepub:uu)cench255 (author)
  • Widersten, MikaelUppsala universitet,Biokemi(Swepub:uu)mikawide (author)
  • Trave, Gilles (author)
  • Nilsson, Mikael T. I.Uppsala universitet,Institutionen för kemi - BMC (author)
  • Jemth, PerUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi(Swepub:uu)pje13912 (author)
  • Uppsala universitetInstitutionen för medicinsk biokemi och mikrobiologi (creator_code:org_t)

Related titles

  • In:Scientific Reports: Springer Science and Business Media LLC52045-2322

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