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

Karlsson, O. Andreas (author): Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi

Ramirez, Juan (author)

Öberg, Daniel (author): Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi

Malmqvist, Tony (author): Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi

Engström, Åke (author): Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi

Friberg, Maria (author): Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi

Chi, Celestine N. (author): Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi

Trave, Gilles (author)

Nilsson, Mikael T. I. (author): Uppsala universitet,Institutionen för kemi - BMC

Jemth, Per (author): Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi

(creator_code:org_t)

2015-03-23
2015
English.
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5

Related links:: https://uu.diva-port... (primary) (Raw object); show more...; https://www.nature.c...; https://urn.kb.se/re...; https://doi.org/10.1...; show less...

Abstract Subject headings

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.

By the author/editor: Karlsson, O. And ...; Ramirez, Juan; Öberg, Daniel; Malmqvist, Tony; Engström, Åke; Friberg, Maria; show more...; Chi, Celestine N ...; Widersten, Mikae ...; Trave, Gilles; Nilsson, Mikael ...; Jemth, Per; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Medical Biotechn ...; and Medical Biotechn ...

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