Structural analysis of human papillomavirus E6 interactions with Scribble PDZ domains.

Autor: Stewart BZ; Department of Biochemistry & Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC, Australia., Caria S; Department of Biochemistry & Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC, Australia., Humbert PO; Department of Biochemistry & Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC, Australia.; Department of Biochemistry & Pharmacology, University of Melbourne, VIC, Australia.; Department of Clinical Pathology, University of Melbourne, VIC, 3010, Australia., Kvansakul M; Department of Biochemistry & Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC, Australia.
Jazyk: angličtina
Zdroj: The FEBS journal [FEBS J] 2023 Jun; Vol. 290 (11), pp. 2868-2880. Date of Electronic Publication: 2023 Jan 18.
DOI: 10.1111/febs.16718
Abstrakt: The cell polarity regulator Scribble has been shown to be a critical regulator of the establishment and development of tissue architecture, and its dysregulation promotes or suppresses tumour development in a context-dependent manner. Scribble activity is subverted by numerous viruses. This includes human papillomaviruses (HPVs), who target Scribble via the E6 protein. Binding of E6 from high-risk HPV strains to Scribble via a C-terminal PDZ-binding motif leads to Scribble degradation in vivo. However, the precise molecular basis for Scribble-E6 interactions remains to be defined. We now show that Scribble PDZ1 and PDZ3 are the major interactors of HPV E6 from multiple high-risk strains, with each E6 protein displaying a unique interaction profile. We then determined crystal structures of Scribble PDZ1 and PDZ3 domains in complex with the PDZ-binding motif (PBM) motifs of E6 from HPV strains 16, 18 and 66. Our findings reveal distinct interaction patterns for each E6 PBM motif from a given HPV strain, suggesting that a complex molecular interplay exists that underpins the overt Scribble-HPV E6 interaction and controls E6 carcinogenic potential.
(© 2023 Federation of European Biochemical Societies.)
Databáze: MEDLINE
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