Structural rearrangements of PDGFRβ in the membrane upon activation by the viral oncoprotein E5.

Authors

Sebastian Otteni, Dirk Windisch, Colin Ziegler, Stephan L Grage, Parvesh Wadhwani, Sergii Afonin, Nermin Kara, Violetta Schneider, Thilo Mast, Torsten H Walther, Anne S Ulrich

Published in

Proceedings of the National Academy of Sciences of the United States of America. Volume 123. Issue 34. Pages e2603552123. Aug 25, 2026. Epub Aug 17, 2026.

Abstract

The transmembrane protein E5 from bovine papillomavirus is the shortest naturally occurring oncoprotein. As a dimer, it activates the platelet-derived growth factor receptor β (PDGFRβ) in a ligand-independent manner by specific helix-helix interactions within the lipid bilayer. For both proteins, we determined the detailed orientations of their transmembrane helices in aligned membrane samples. Solid-state ¹⁵N-NMR was used to study either protein segment alone, as well as in the heterocomplex. Remarkably, the assembly of E5 with PDGFRβ led to structural rearrangements of both partners. Binding of E5 triggers a rotation of the PDGFRβ helices around their axes. At the same time, the E5 helices rotate in the membrane to expose Gln17 as well as Asp33, allowing their respective interaction with Thr513 and Lys499 on PDGFRβ. Based on these distinct membrane orientations, we present structural models of the heteromeric E5-PDGFRβ complex, and a mechanism for oncogenic receptor activation.

PMID:
42607206
Bibliographic data and abstract were imported from PubMed on 18 Aug 2026.

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