The goal of the proposed research is to investigate the structural biology of the proteins that bind and transport heavy metals ions. Proteins from the bacterial mercury detoxification system are the principal objects of this study. There is a direct molecular connection between the mechanism by which bacteria detoxify heavy metals and a number of diseases, because of the high level of homology among many proteins responsible for binding heavy metals in bacteria and humans. The immediate goal of the research is to determine detailed structures of the membrane proteins MerT and MerF, responsible for transport of the Hg(II) ions in the cell, where reduction to Hg(O) occurs. We intend to do so by using Nuclear Magnetic Resonance (NMR) spectroscopy. Solving this problem will concurrently be instrumental to the development of a general methodology for structure determination of membrane proteins. The structures of the proteins that bind and transport heavy metals in bacteria will provide a molecular model to understand diseases related to improper heavy metal transport and to exposure to heavy metal toxins.
| De Angelis, Anna A; Opella, Stanley J (2007) Bicelle samples for solid-state NMR of membrane proteins. Nat Protoc 2:2332-8 |
| Grant, Christopher V; Sit, Siu-Ling; De Angelis, Anna A et al. (2007) An efficient (1)H/(31)P double-resonance solid-state NMR probe that utilizes a scroll coil. J Magn Reson 188:279-84 |
| Park, Sang Ho; Prytulla, Stefan; De Angelis, Anna A et al. (2006) High-resolution NMR spectroscopy of a GPCR in aligned bicelles. J Am Chem Soc 128:7402-3 |
| De Angelis, Anna A; Howell, Stanley C; Opella, Stanley J (2006) Assigning solid-state NMR spectra of aligned proteins using isotropic chemical shifts. J Magn Reson 183:329-32 |
| Park, Sang Ho; De Angelis, Anna A; Nevzorov, Alexander A et al. (2006) Three-dimensional structure of the transmembrane domain of Vpu from HIV-1 in aligned phospholipid bicelles. Biophys J 91:3032-42 |
| De Angelis, Anna A; Howell, Stanley C; Nevzorov, Alexander A et al. (2006) Structure determination of a membrane protein with two trans-membrane helices in aligned phospholipid bicelles by solid-state NMR spectroscopy. J Am Chem Soc 128:12256-67 |
| Sinha, Neeraj; Grant, Christopher V; Wu, Chin H et al. (2005) SPINAL modulated decoupling in high field double- and triple-resonance solid-state NMR experiments on stationary samples. J Magn Reson 177:197-202 |
| De Angelis, A A; Jones, D H; Grant, C V et al. (2005) NMR experiments on aligned samples of membrane proteins. Methods Enzymol 394:350-82 |
| De Angelis, Anna A; Nevzorov, Alexander A; Park, Sang Ho et al. (2004) High-resolution NMR spectroscopy of membrane proteins in aligned bicelles. J Am Chem Soc 126:15340-1 |
