The long-term goal of this project is to understand the molecular mechanism of translation in terms of the three-dimensional structure of the ribosome and its interactions with its functional ligands. The purpose is to determine the structure of Thermus thermophilus 70S ribosomes, in complex with mRNA, tRNAs and translational factors in different states of the translational elongation cycle. The immediate goal is to study several functional co-crystal complexes at medium (ca. 9Angstrom units) resolution. The longer-term plan is to then focus on the most promising candidate for solution at much higher (ca. 3Angstrom units) resolution. It is expected that these results will not only provide a sound structural basis for understanding the mechanism of translation at the molecular level, but will also reveal a wealth of information about RNA structure and protein-RNA interactions in general.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM059140-04
Application #
6519977
Study Section
Biophysical Chemistry Study Section (BBCB)
Program Officer
Flicker, Paula F
Project Start
1999-04-01
Project End
2004-03-31
Budget Start
2002-04-01
Budget End
2004-03-31
Support Year
4
Fiscal Year
2002
Total Cost
$439,731
Indirect Cost
Name
University of California Santa Cruz
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
City
Santa Cruz
State
CA
Country
United States
Zip Code
95064
Noller, Harry F (2017) The parable of the caveman and the Ferrari: protein synthesis and the RNA world. Philos Trans R Soc Lond B Biol Sci 372:
Mohan, Srividya; Noller, Harry F (2017) Recurring RNA structural motifs underlie the mechanics of L1 stalk movement. Nat Commun 8:14285
Colussi, Timothy M; Costantino, David A; Zhu, Jianyu et al. (2015) Initiation of translation in bacteria by a structured eukaryotic IRES RNA. Nature 519:110-3
Mohan, Srividya; Donohue, John Paul; Noller, Harry F (2014) Molecular mechanics of 30S subunit head rotation. Proc Natl Acad Sci U S A 111:13325-30
Zhou, Jie; Lancaster, Laura; Donohue, John Paul et al. (2014) How the ribosome hands the A-site tRNA to the P site during EF-G-catalyzed translocation. Science 345:1188-91
Ramrath, David J F; Lancaster, Laura; Sprink, Thiemo et al. (2013) Visualization of two transfer RNAs trapped in transit during elongation factor G-mediated translocation. Proc Natl Acad Sci U S A 110:20964-9
Zhou, Jie; Lancaster, Laura; Donohue, John Paul et al. (2013) Crystal structures of EF-G-ribosome complexes trapped in intermediate states of translocation. Science 340:1236086
Santos, Natalia; Zhu, Jianyu; Donohue, John Paul et al. (2013) Crystal structure of the 70S ribosome bound with the Q253P mutant form of release factor RF2. Structure 21:1258-63
Zhou, Jie; Lancaster, Laura; Trakhanov, Sergei et al. (2012) Crystal structure of release factor RF3 trapped in the GTP state on a rotated conformation of the ribosome. RNA 18:230-40
Zhou, Jie; Korostelev, Andrei; Lancaster, Laura et al. (2012) Crystal structures of 70S ribosomes bound to release factors RF1, RF2 and RF3. Curr Opin Struct Biol 22:733-42

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