Structural Studies of AIDS Proteins by NMR

Groneborn, A M.

Abstract

Work has been carried out on a number of structural problems related to proteins derived from the HIV virus. These include the RNAse H domain of HIV-1 reverse transcriptase, the p7 nucleocapsid protein of HIV-1, and proteins of the immune system, in particular interleukin- 1beta and the double zinc finger domain of the human enhancer binding protein. The secondary structure of the RNaseH domain has been determined using double and triple resonance 3D NMR spectroscopy, and current work is being focused on studying its internal dynamics and obtaining a three-dimensional structure in solution. The solution structure of the zinc finger domains of the p7 nucleocapsid protein has been determined, and the two zinc binding domains shown to be identical within the errors of the coordinates. The high resolution structure of interleukin-1beta in solution has been determined using 3D and 4D heteronuclear NMR. In addition, structural studies have begun on the double zinc finger domain of the human enhancer protein which binds specifically to the regulatory region in the long terminal repeat of the HIV genome.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Type: Intramural Research (Z01)
• Project #: 1Z01DK029022-04
• Application #: 3854793
• Support Year: 4
• Fiscal Year: 1991

Institution

• Name: National Institute of Diabetes and Digestive and Kidney Diseases
• Country: United States

Publications

Barrientos, Laura G; Gronenborn, Angela M (2005) The highly specific carbohydrate-binding protein cyanovirin-N: structure, anti-HIV/Ebola activity and possibilities for therapy. Mini Rev Med Chem 5:21-31

Ding, Keyang; Gronenborn, Angela M (2004) Sensitivity-enhanced IPAP experiments for measuring one-bond 13C'-13Calpha and 13Calpha-1Halpha residual dipolar couplings in proteins. J Magn Reson 167:253-8

Barrientos, Laura G; Lasala, Fatima; Delgado, Rafael et al. (2004) Flipping the switch from monomeric to dimeric CV-N has little effect on antiviral activity. Structure 12:1799-807

Ding, Keyang; Gronenborn, Angela M (2004) Protein Backbone 1H(N)-13Calpha and 15N-13Calpha residual dipolar and J couplings: new constraints for NMR structure determination. J Am Chem Soc 126:6232-3

Barrientos, Laura G; O'Keefe, Barry R; Bray, Mike et al. (2003) Cyanovirin-N binds to the viral surface glycoprotein, GP1,2 and inhibits infectivity of Ebola virus. Antiviral Res 58:47-56

Ding, Keyang; Gronenborn, Angela M (2003) Simultaneous and accurate determination of one-bond (15)N-(13)C' and two-bond (1)H(N)--(13)C' dipolar couplings. J Am Chem Soc 125:11504-5

Ishima, Rieko; Torchia, Dennis A; Lynch, Shannon M et al. (2003) Solution structure of the mature HIV-1 protease monomer: insight into the tertiary fold and stability of a precursor. J Biol Chem 278:43311-9

Louis, John M; Ishima, Rieko; Nesheiwat, Issa et al. (2003) Revisiting monomeric HIV-1 protease. Characterization and redesign for improved properties. J Biol Chem 278:6085-92

Katoh, Etsuko; Louis, John M; Yamazaki, Toshimasa et al. (2003) A solution NMR study of the binding kinetics and the internal dynamics of an HIV-1 protease-substrate complex. Protein Sci 12:1376-85

Barrientos, Laura G; Louis, John M; Ratner, Daniel M et al. (2003) Solution structure of a circular-permuted variant of the potent HIV-inactivating protein cyanovirin-N: structural basis for protein stability and oligosaccharide interaction. J Mol Biol 325:211-23