We will investigate the co-adaptations of seryl-tRNA synthetase (SerRS), a well studied class II aminoacyl-tRNA synthetase, with tRNAs through evolution. The availability of many genomic sequences enables us to clone the genes encoding SerRS enzymes from the different taxonomic domains. During the previous NIH-FIRCA grant (supporting the collaboration with Dr. Ivana Weygand-Durasevic), we focused on identifying the differences in tRNA:aminoacyl-tRNA synthetase specificities characteristic for the distinct protein synthesizing compartments of eukaryotic cells (mitochondria and chloroplasts). Until recently, the study of aminoacyl-tRNA synthesis in archaea had received little attention. The sequencing of the first archaeal genome (Methanococcus jannaschii) revealed the """"""""lack"""""""" of few canonical aminoacyl-tRNA synthetases, including the one specific for serine. However, biochemical analysis of purified and heterologously expressed SerRS-encoding (serS) genes from two other methanogens, Methanoacterium thermoautotrophicum and Methanococcus maripaludis, showed that these proteins are SerRS enzymes. Thus, there are three types of SerRS found in the archaea. The enzyme from the halophilic archaeon Haloarcula marismortui has high sequence similarity to bacterial SerRS proteins, while phylogenetic analyses revealed in other archaea a different clade with sequence similarity to the eukaryotic enzymes. In contrast, the three methanogenic archaea contain genes that display only low sequence similarity to the known serS genes from all other organisms and encode a structurally uncommon enzyme. In the proposed project we will pursue detailed biochemical, mutational, and structural studies with the aim of elucidating the structure-function relationships in these unusual seryl-tRNA synthetases. These studies will complement our ongoing projects on the identification and characterization of components involved in aminoacyl-tRNA synthesis in the living kingdom.

Agency
National Institute of Health (NIH)
Institute
Fogarty International Center (FIC)
Type
Small Research Grants (R03)
Project #
5R03TW001467-02
Application #
6499499
Study Section
International and Cooperative Projects 1 Study Section (ICP)
Program Officer
Katz, Flora N
Project Start
2001-02-09
Project End
2004-01-31
Budget Start
2002-02-01
Budget End
2003-01-31
Support Year
2
Fiscal Year
2002
Total Cost
$38,760
Indirect Cost
Name
Yale University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520