Molecular Examination of the Transmembrane Requirements of the Platelet-derived Growth Factor β Receptor for a Productive Interaction with the Bovine Papillomavirus E5 Oncoprotein
Journal of Biological Chemistry
The small transmembrane E5 protein of bovine papillomavirus (BPV) transforms cells by forming a stable complex with and activating the platelet-derived growth factor ␤ receptor (PDGF␤R). The E5/PDGF␤R interaction is thought to involve specific physical contacts between the transmembrane domains of the two proteins. Lys 499 at the extracellular juxtamembrane position and Thr 513 within the transmembrane domain of the PDGF␤R are required for the interaction and are predicted to contact
... contact analogously positioned residues in the E5 protein. Here, mutagenic analysis of the transmembrane region of the PDGF␤R was performed to further characterize the nature of the E5/PDGF␤R interaction. We show that the receptor transmembrane domain, with minimal extracellular and intracellular sequence, is sufficient for the interaction. In addition, we provide evidence that the polar nature of Thr 513 as well as its positioning along the transmembrane ␣-helix is important for the interaction. We also identify the receptor transmembrane amino acids Ile 506 and Leu 520 as additional requirements for the interaction. Because Lys 499 , Thr 513 , Ile 506 , and Leu 520 all align along the same face of the predicted PDGF␤R transmembrane ␣-helix, our data support the model that the PDGF␤R contacts the E5 protein via multiple amino acids along a single ␣-helical interface.