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Conformational chan...
Conformational change and non-canonical interactions in the complex between human papillomavirus E6 protein and Synapse-Associated Protein 97
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- Chi, Celestine N. (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Per Jemth
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- Bach, Anders (author)
- University of Copenhagen
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- Engström, Åke (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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- Strømgaard, Kristian (author)
- University of Copenhagen
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- Lundström, Patrik (author)
- University of Linköping
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- Ferguson, Neil (author)
- 4UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin
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- Jemth, Per (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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(creator_code:org_t)
- English.
- Related links:
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https://urn.kb.se/re...
Abstract
Subject headings
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- The E6 protein of human papillomavirus exhibits complex interaction patterns with several host proteins and their roles in HPV mediated oncogensis have proved challenging to study. Here we use several biophysical techniques to explore the binding of E6 to the three PDZ domains of the tumor suppressor protein SAP97. All potential binding sites in SAP97 can bind E6 with low micromolar affinity. Unexpectedly,binding is not mutually exclusive and all three PDZ domains can simultaneously bind E6. Intriguingly, the quaternary complex has the same apparent hydrodynamic volume as the unliganded PDZ region, despite having a doubled mass, suggesting that a conformational change occurs in the PDZ region upon E6 binding. Further, using NMR, we discovered a new mode of interaction between E6 and PDZ, as a subset of residues distal to the binding pocket in the PDZ2 domain was found to exhibit non-canonical interactions with the E6 protein suggesting that a large proportion of the proteins surface defines binding specificity
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
Keyword
- cervical cancer
- NMR
- kinetics
- HPV
- SAP97
- isothermal calorimetry
- Biochemistry
- Biokemi
- Biokemi
- Biochemistry
Publication and Content Type
- ref (subject category)
- art (subject category)
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