Investigations of Macromolecular Structures and Dynamics in Solution by NMR

Gronenborn, A M.

Abstract

The objective of the overall research in this laboratory is centered on achieving as complete a description as possible for the structures of peptides, proteins, nucleic acids and their complexes in solution, principally by NMR spectroscopy. At present particular emphasis is being placed on developing approaches which allow the investigation of larger and complex systems as well as increase the precision with which these solution structures can be obtained, studies aimed at correlating structure and function, and experiments aimed at investigating protein folding. Structural studies for several proteins have been carried out. These DNA binding domains of Mu Transposase, the N-terminal domain of HIV-1 integrase G. In addition, work was also carried out on a number of protein nucleic acid complexes, including those of GAGA, Are A and HMG-I/Y. Also mutant core libraries of streptococcal Protein G have been prepared and characterized structurally as well as with respect to stability. One of the largest systems whose structure we determined by NMR is the N-terminal domain of Enzyme I of the PTS pathway. In addition, the binding surface for Hpr ou EI was determined and structural implications of phosphorylation investigated.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Type: Intramural Research (Z01)
• Project #: 1Z01DK029025-08
• Application #: 6161937
• Study Section: Special Emphasis Panel (LCP)
• Support Year: 8
• Fiscal Year: 1997

Institution

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

Publications

Louis, John M; Byeon, In-Ja L; Baxa, Ulrich et al. (2005) The GB1 amyloid fibril: recruitment of the peripheral beta-strands of the domain swapped dimer into the polymeric interface. J Mol Biol 348:687-98

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

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

Dangi, Bindi; Gronenborn, Angela M; Rosner, Judah L et al. (2004) Versatility of the carboxy-terminal domain of the alpha subunit of RNA polymerase in transcriptional activation: use of the DNA contact site as a protein contact site for MarA. Mol Microbiol 54:45-59

Ding, Keyang; Louis, John M; Gronenborn, Angela M (2004) Insights into conformation and dynamics of protein GB1 during folding and unfolding by NMR. J Mol Biol 335:1299-307

Byeon, In-Ja L; Louis, John M; Gronenborn, Angela M (2004) A captured folding intermediate involved in dimerization and domain-swapping of GB1. J Mol Biol 340:615-25

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

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