3FRX

Crystal Structure of the Yeast Orthologue of RACK1, Asc1.

Summary for 3FRX

• Entry DOI: 10.2210/pdb3frx/pdb
• Descriptor: Guanine nucleotide-binding protein subunit beta-like protein, MANGANESE (II) ION (3 entities in total)
• Functional Keywords: rack1, wd40, beta propeller, ribosome, translation, acetylation, cytoplasm, phosphoprotein, wd repeat, signaling protein
• Biological source: Saccharomyces cerevisiae (yeast)
• Cellular location: Cytoplasm: P38011
• Total number of polymer chains: 4
• Total formula weight: 140897.67

Authors

Coyle, S.M.,Gilbert, W.V.,Doudna, J.A. (deposition date: 2009-01-08, release date: 2009-02-17, Last modification date: 2024-10-30)

Primary citation

Coyle, S.M.,Gilbert, W.V.,Doudna, J.A.
Direct link between RACK1 function and localization at the ribosome in vivo
Mol.Cell.Biol., 29:1626-1634, 2009

PubMed Abstract: The receptor for activated C-kinase (RACK1), a conserved protein implicated in numerous signaling pathways, is a stoichiometric component of eukaryotic ribosomes located on the head of the 40S ribosomal subunit. To test the hypothesis that ribosome association is central to the function of RACK1 in vivo, we determined the 2.1-A crystal structure of RACK1 from Saccharomyces cerevisiae (Asc1p) and used it to design eight mutant versions of RACK1 to assess roles in ribosome binding and in vivo function. Conserved charged amino acids on one side of the beta-propeller structure were found to confer most of the 40S subunit binding affinity, whereas an adjacent conserved and structured loop had little effect on RACK1-ribosome association. Yeast mutations that confer moderate to strong defects in ribosome binding mimic some phenotypes of a RACK1 deletion strain, including increased sensitivity to drugs affecting cell wall biosynthesis and translation elongation. Furthermore, disruption of RACK1's position at the 40S ribosomal subunit results in the failure of the mRNA binding protein Scp160 to associate with actively translating ribosomes. These results provide the first direct evidence that RACK1 functions from the ribosome, implying a physical link between the eukaryotic ribosome and cell signaling pathways in vivo.

PubMed: 19114558
DOI: 10.1128/MCB.01718-08

Experimental method

X-RAY DIFFRACTION (2.13 Å)