GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:10983975

From GONUTS
Jump to: navigation, search
Citation

Dong, J, Qiu, H, Garcia-Barrio, M, Anderson, J and Hinnebusch, AG (2000) Uncharged tRNA activates GCN2 by displacing the protein kinase moiety from a bipartite tRNA-binding domain. Mol. Cell 6:269-79

Abstract

Protein kinase GCN2 regulates translation in amino acid-starved cells by phosphorylating elF2. GCN2 contains a regulatory domain related to histidyl-tRNA synthetase (HisRS) postulated to bind multiple deacylated tRNAs as a general sensor of starvation. In accordance with this model, GCN2 bound several deacylated tRNAs with similar affinities, and aminoacylation of tRNAphe weakened its interaction with GCN2. Unexpectedly, the C-terminal ribosome binding segment of GCN2 (C-term) was required in addition to the HisRS domain for strong tRNA binding. A combined HisRS+ C-term segment bound to the isolated protein kinase (PK) domain in vitro, and tRNA impeded this interaction. An activating mutation (GCN2c-E803V) that weakens PK-C-term association greatly enhanced tRNA binding by GCN2. These results provide strong evidence that tRNA stimulates the GCN2 kinase moiety by preventing an inhibitory interaction with the bipartite tRNA binding domain.

Links

PubMed

Keywords

Binding Sites; DNA-Binding Proteins/metabolism; Eukaryotic Initiation Factor-2/metabolism; Gene Expression Regulation; Histidine-tRNA Ligase/chemistry; Lysine; Protein Biosynthesis; Protein Kinases/chemistry; Protein Kinases/metabolism; Protein-Serine-Threonine Kinases; RNA, Transfer, Amino Acid-Specific/metabolism; RNA, Transfer, Phe/metabolism; Recombinant Proteins/chemistry; Recombinant Proteins/metabolism; Ribosomes/metabolism; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae Proteins

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

YEAST:GCN2

involved_in

GO:0140469: GCN2-mediated signaling

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

YEAST:GCN2

enables

GO:0000049: tRNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

YEAST:GCN2

involved_in

GO:0046777: protein autophosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

YEAST:GCN2

involved_in

GO:0006468: protein phosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

YEAST:GCN2

enables

GO:0004672: protein kinase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

YEAST:GCN2

enables

GO:0043022: ribosome binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

YEAST:GCN2

enables

GO:0043621: protein self-association

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

YEAST:GCN2

enables

GO:0042803: protein homodimerization activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

YEAST:GCN2

involved_in

GO:0060733: regulation of eIF2 alpha phosphorylation by amino acid starvation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.