Abstract

The objective is to understand how proteins recognize specific sequences of double stranded DNA and to understand how the activities of gene regulatory proteins are controlled by interactions with other proteins. Genetic, biochemical, and structural studies will be used to elucidate the detailed mechanism by which the Arc and Mnt repressors of bacteriophage P22 bind to their respective operator sequences, and to characterize mutations that enhance or alter the binding specificity of the lambda repressor and lambda Cro proteins. Mutations that abolish or enhance cooperative interactions between lambda repressor molecules bound at adjacent operator sites will also be isolated, and the effects of these mutations on protein-mediated DNA looping and the linear polymerization of repressor in solution will be determined. Finally, the mechanisms of RecA-mediated and P22 antirepressor-mediated inactivation of lambda repressor will be explored by studying the biochemical properties of mutant proteins that display altered properties in the inactivation reactions.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI016892-10
Application #
3126889
Study Section
Microbial Physiology and Genetics Subcommittee 2 (MBC)
Project Start
1980-04-01
Project End
1993-03-31
Budget Start
1989-04-01
Budget End
1990-03-31
Support Year
10
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
Massachusetts Institute of Technology
Department
Type
Schools of Arts and Sciences
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02139

  Publications

Hari, Sanjay B; Grant, Robert A; Sauer, Robert T (2018) Structural and Functional Analysis of E. coli Cyclopropane Fatty Acid Synthase. Structure 26:1251-1258.e3
Brown, Breann L; Kardon, Julia R; Sauer, Robert T et al. (2018) Structure of the Mitochondrial Aminolevulinic Acid Synthase, a Key Heme Biosynthetic Enzyme. Structure 26:580-589.e4
Amberg-Johnson, Katherine; Hari, Sanjay B; Ganesan, Suresh M et al. (2017) Small molecule inhibition of apicomplexan FtsH1 disrupts plastid biogenesis in human pathogens. Elife 6:
Totaro, Kyle A; Barthelme, Dominik; Simpson, Peter T et al. (2017) Rational Design of Selective and Bioactive Inhibitors of the Mycobacterium tuberculosis Proteasome. ACS Infect Dis 3:176-181
Baytshtok, Vladimir; Chen, Jiejin; Glynn, Steven E et al. (2017) Covalently linked HslU hexamers support a probabilistic mechanism that links ATP hydrolysis to protein unfolding and translocation. J Biol Chem 292:5695-5704
Olivares, Adrian O; Baker, Tania A; Sauer, Robert T (2016) Mechanistic insights into bacterial AAA+ proteases and protein-remodelling machines. Nat Rev Microbiol 14:33-44
Hari, Sanjay B; Sauer, Robert T (2016) The AAA+ FtsH Protease Degrades an ssrA-Tagged Model Protein in the Inner Membrane of Escherichia coli. Biochemistry 55:5649-5652
Stein, Benjamin J; Grant, Robert A; Sauer, Robert T et al. (2016) Structural Basis of an N-Degron Adaptor with More Stringent Specificity. Structure 24:232-42
Baytshtok, Vladimir; Fei, Xue; Grant, Robert A et al. (2016) A Structurally Dynamic Region of the HslU Intermediate Domain Controls Protein Degradation and ATP Hydrolysis. Structure 24:1766-1777
Barthelme, Dominik; Sauer, Robert T (2016) Origin and Functional Evolution of the Cdc48/p97/VCP AAA+ Protein Unfolding and Remodeling Machine. J Mol Biol 428:1861-9

Showing the most recent 10 out of 156 publications