Interactions between transmembrane helices are a major feature of the architecture of membrane proteins. Understanding the principles that guide such interactions will illuminate membrane protein folding, stability, and oligomer formation. Since membrane proteins are coded by more than 20% of all genes and are the targets of more than half of all drugs, such an understanding will be both enlightening and useful. We will work towards understanding the motifs and interactions that give rise to transmembrane helix (TM) interactions that stabilize protein structures in biological membranes, and to begin to connect our understanding to biological functions. We have developed a diverse toolkit for the study of TM interactions, including: (a) genetic and biochemical assays in micelles, bilayers and membranes, (b) computational approaches, and (c) structural studies using optical spectroscopy and NMR. Our approach will have several major divisions: a study of TM trimers in HIV gp41 TMs and MHC li; an effort to find the link between helix dimerization and signaling; a study of interaction motifs; an improvement of TM-TM computational methods; and tests of the principles and motifs that can be identified in helix associations. ? ?
| Vila-Viçosa, Diogo; Silva, Tomás F D; Slaybaugh, Gregory et al. (2018) Membrane-Induced p Ka Shifts in wt-pHLIP and Its L16H Variant. J Chem Theory Comput 14:3289-3297 |
| Wyatt, Linden C; Lewis, Jason S; Andreev, Oleg A et al. (2018) Applications of pHLIP Technology for Cancer Imaging and Therapy: (Trends in Biotechnology 35, 653-664, 2017). Trends Biotechnol 36:1300 |
| Karabadzhak, Alexander G; Weerakkody, Dhammika; Deacon, John et al. (2018) Bilayer Thickness and Curvature Influence Binding and Insertion of a pHLIP Peptide. Biophys J 114:2107-2115 |
| Wyatt, Linden C; Moshnikova, Anna; Crawford, Troy et al. (2018) Peptides of pHLIP family for targeted intracellular and extracellular delivery of cargo molecules to tumors. Proc Natl Acad Sci U S A 115:E2811-E2818 |
| Daniels, Jennifer L; Crawford, Troy M; Andreev, Oleg A et al. (2017) Synthesis and characterization of pHLIP® coated gold nanoparticles. Biochem Biophys Rep 10:62-69 |
| 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 |
| Wyatt, Linden C; Lewis, Jason S; Andreev, Oleg A et al. (2017) Applications of pHLIP Technology for Cancer Imaging and Therapy. Trends Biotechnol 35:653-664 |
| Shrestha, Samana; Cooper, Leon N; Andreev, Oleg A et al. (2016) Gold Nanoparticles for Radiation Enhancement in Vivo. Jacobs J Radiat Oncol 3: |
| Weerakkody, Dhammika; Andreev, Oleg A; Reshetnyak, Yana K (2016) Insertion into lipid bilayer of truncated pHLIP®peptide. Biochem Biophys Rep 8:290-295 |
| Svoronos, Alexander A; Engelman, Donald M; Slack, Frank J (2016) OncomiR or Tumor Suppressor? The Duplicity of MicroRNAs in Cancer. Cancer Res 76:3666-70 |
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