The Program is directed at structural studies of macromolecules, a macromolecular assemblies, and cell organelles such as ribosomes and plasma membranes. The major techniques to be employed center on X-ray diffraction from single crystals or from solutions or partially ordered systems; on high resolution solution NMR; on a whole range of other biophysical techniques, including mass spectroscopy, either by themselves or in combination with chemical labeling procedures. In addition to the time-average structures, which are the most immediate output of the diffraction work, the Program will be especially aimed at studying the relative motion of various parts (domains) of the polymer chains and of the subunits with respect to each other in the larger aggregates. Motion can, in part, be inferred from different static structures that can be determined under varied conditions of environment and ligation. Of special interest is the motion during: 1) the catalytic cycles of polymerases along their nucleic acid templates and substrates; 2) the rearrangement of protein subunits during the ligand-regulated formation of specific protein/DNA complexes and of the complexes themselves during DNA recombination; 3) the movement of ribosomes on the message during the translocation step of protein synthesis; and 4) the secretion of polypeptide chains into and through the membrane bilayer. The theoretical approaches will include free-energy perturbation calculations on various systems, modeling of protein-DNA and protein-membrane interactions, modeling the macromolecule-solvent interface, and continuing improvement of the structure refinement procedures for both X-ray and NMR data.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
5P01GM022778-24
Application #
2900504
Study Section
Special Emphasis Panel (ZRG7-SSS-Z (07))
Project Start
1976-04-01
Project End
2001-03-31
Budget Start
1999-04-01
Budget End
2000-03-31
Support Year
24
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Yale University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
Wang, Jimin; Liu, Zheng; Crabtree, Robert H et al. (2018) On the damage done to the structure of the Thermoplasma acidophilum proteasome by electron radiation. Protein Sci 27:2051-2061
Sherlock, Madeline E; Sadeeshkumar, Harini; Breaker, Ronald R (2018) Variant Bacterial Riboswitches Associated with Nucleotide Hydrolase Genes Sense Nucleoside Diphosphates. Biochemistry :
Harris, Kimberly A; Zhou, Zhiyuan; Peters, Michelle L et al. (2018) A second RNA-binding protein is essential for ethanol tolerance provided by the bacterial OLE ribonucleoprotein complex. Proc Natl Acad Sci U S A 115:E6319-E6328
Greenlee, Etienne B; Stav, Shira; Atilho, Ruben M et al. (2018) Challenges of ligand identification for the second wave of orphan riboswitch candidates. RNA Biol 15:377-390
Mirihana Arachchilage, Gayan; Sherlock, Madeline E; Weinberg, Zasha et al. (2018) SAM-VI RNAs selectively bind S-adenosylmethionine and exhibit similarities to SAM-III riboswitches. RNA Biol 15:371-378
Wang, Jimin (2018) Determination of chemical identity and occupancy from experimental density maps. Protein Sci 27:411-420
Sherlock, Madeline E; Sudarsan, Narasimhan; Breaker, Ronald R (2018) Riboswitches for the alarmone ppGpp expand the collection of RNA-based signaling systems. Proc Natl Acad Sci U S A 115:6052-6057
Harris, Kimberly A; Breaker, Ronald R (2018) Large Noncoding RNAs in Bacteria. Microbiol Spectr 6:
Yang, Yang; Kang, Dongwei; Nguyen, Laura A et al. (2018) Structural basis for potent and broad inhibition of HIV-1 RT by thiophene[3,2-d]pyrimidine non-nucleoside inhibitors. Elife 7:
Sherlock, Madeline E; Breaker, Ronald R (2017) Biochemical Validation of a Third Guanidine Riboswitch Class in Bacteria. Biochemistry 56:359-363

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