In this competing renewal application of a Merit award, Dr. DiMaio describes a series of experiments to investigate various aspects of the interaction between the bovine papillomavirus type 1 (BPV-1) E5 protein and the cellular PDGF beta receptor. Based upon studies performed during the prior funding period, Dr. DiMaio has proposed a model to explain how the E5 protein forms a dimer and binds to the PDGF beta receptor, and how this interaction results in receptor activation that contributes to cellular transformation.
Six aims are proposed: 1) to determine the molecular basis for the ability of E5 to discriminate between the PDGF beta receptor and = the closely related PDGF alpha receptor. 2) To identify the helical interface that mediates E5 dimerization, 3) to test the model that each E5 monomer contributes to the productive binding of E5 dimer to PDGF beta, 4) to characterize the signaling that occurs as a consequence of E5's activation of the PDGF beta receptor, 5) to test the hypothesis that certain mutants of E5 can interfere with PDGF beta signaling and 6) to identify novel peptide sequences that can contribute to the multimerization and activation of PDGF beta receptor
| Petti, Lisa M; Marlatt, Sara A; Luo, Yong et al. (2018) Regulation of C-C chemokine receptor 5 (CCR5) stability by Lys197 and by transmembrane protein aptamers that target it for lysosomal degradation. J Biol Chem 293:8787-8801 |
| He, Li; Steinocher, Helena; Shelar, Ashish et al. (2017) Single methyl groups can act as toggle switches to specify transmembrane Protein-protein interactions. Elife 6: |
| Karabadzhak, Alexander G; Petti, Lisa M; Barrera, Francisco N et al. (2017) Two transmembrane dimers of the bovine papillomavirus E5 oncoprotein clamp the PDGF ? receptor in an active dimeric conformation. Proc Natl Acad Sci U S A 114:E7262-E7271 |
| DiMaio, Daniel (2016) Thank You, Edward. Merci, Louis. PLoS Pathog 12:e1005320 |
| Heim, Erin N; Marston, Jez L; Federman, Ross S et al. (2015) Biologically active LIL proteins built with minimal chemical diversity. Proc Natl Acad Sci U S A 112:E4717-25 |
| Cohen, Emily B; Jun, Susan J; Bears, Zachary et al. (2014) Mapping the homodimer interface of an optimized, artificial, transmembrane protein activator of the human erythropoietin receptor. PLoS One 9:e95593 |
| Dimaio, Daniel (2014) Is virology dead? MBio 5:e01003-14 |
| DiMaio, Daniel (2014) Viral miniproteins. Annu Rev Microbiol 68:21-43 |
| Chacón, Kelly M; Petti, Lisa M; Scheideman, Elizabeth H et al. (2014) De novo selection of oncogenes. Proc Natl Acad Sci U S A 111:E6-E14 |
| DiMaio, Daniel; Petti, Lisa M (2013) The E5 proteins. Virology 445:99-114 |
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