Abstract

The overall goals of the Opella Component of the Program Project are to develop generally applicable NMR methods for determining the structures and describing the dynamics of membrane proteins, and to apply these methods to Vpu in membrane environments. The availability of uniformly isotopically labeled Vpu in the model membranes of micelles, bicelles, and bilayers enables multidimensional solution NMR and solid-state NMR experiments to be utilized for determining the structure and describing the dynamics of Vpu over a wide range of timescales. The NMR studies are an integral part of the broadly based approach to describing the structural and function of Vpu presented in this proposal, which includes all of the major experimental and theoretical methods available for the characterization of proteins. The results will be directly applied in the development of drugs to interfere with the functions of Vpu and the virus lifecycle as we seek effective treatments for AIDS.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
3P01GM056538-01S1
Application #
2756065
Study Section
Project Start
Project End
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
University of Pennsylvania
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

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
Kochendoerfer, Gerd G; Jones, David H; Lee, Sangwon et al. (2004) Functional characterization and NMR spectroscopy on full-length Vpu from HIV-1 prepared by total chemical synthesis. J Am Chem Soc 126:2439-46
Becker, Christian F W; Oblatt-Montal, Myrta; Kochendoerfer, Gerd G et al. (2004) Chemical synthesis and single channel properties of tetrameric and pentameric TASPs (template-assembled synthetic proteins) derived from the transmembrane domain of HIV virus protein u (Vpu). J Biol Chem 279:17483-9
Mesleh, M F; Valentine, K G; Opella, S J et al. (2003) Myristoylation as a general method for immobilization and alignment of soluble proteins for solid-state NMR structural studies. J Biomol NMR 25:55-61
Sun, Feng (2003) Molecular dynamics simulation of human immunodeficiency virus protein U (Vpu) in lipid/water Langmuir monolayer. J Mol Model 9:114-23
Mesleh, Michael F; Opella, Stanley J (2003) Dipolar Waves as NMR maps of helices in proteins. J Magn Reson 163:288-99
Marassi, Francesca M; Opella, Stanley J (2003) Simultaneous assignment and structure determination of a membrane protein from NMR orientational restraints. Protein Sci 12:403-11
Zheng, Songyan; Strzalka, Joseph; Jones, David H et al. (2003) Comparative structural studies of Vpu peptides in phospholipid monolayers by x-ray scattering. Biophys J 84:2393-415
Opella, Stanley J (2003) Membrane protein NMR studies. Methods Mol Biol 227:307-20
Montal, M (2003) Structure-function correlates of Vpu, a membrane protein of HIV-1. FEBS Lett 552:47-53

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