Structural analysis of ribosomal RACK1 and its role in translational control.
Receptor for Activated C-Kinase 1 (RACK1) belongs to the WD40 family of proteins, known to act as scaffolding proteins in interaction networks. Accordingly, RACK1 is found to have numerous interacting partners ranging from kinases and signaling proteins to membrane bound receptors and ion channels. Interestingly, RACK1 has also been identified as a ribosomal protein present in all eukaryotic ribosomes. Structures of eukaryotic ribosomes have shown RACK1 to be located at the back of the head of the small ribosomal subunit. This suggests that RACK1 could act as a ribosomal scaffolding protein recruiting regulators of translation to the ribosome, and several studies have in fact found RACK1 to play a role in regulation of translation. To fully understand the role of RACK1 we need to understand whether the many reported interaction partners of RACK1 bind to free or ribosomal RACK1. In this review we provide a structural analysis of ribosome-bound RACK1 to provide a basis for answering this fundamental question. Our analysis shows that RACK1 is tightly bound to the ribosome through highly conserved and specific interactions confirming RACK1 as an integral ribosomal protein. Furthermore, we have analyzed whether reported binding sites for RACK1 interacting partners with a proposed role in translational control are accessible on ribosomal RACK1. Our analysis shows that most of the interaction partners with putative regulatory functions have binding sites that are available on ribosomal RACK1, supporting the role of RACK1 as a ribosomal signaling hub. We also discuss the possible role for RACK1 in recruitment of ribosomes to focal adhesion sites and regulation of local translation during cell spreading and migration.
Department of Molecular Biology and Genetics, Gustav Wieds Vej 10C, DK-8000 Aarhus C, Aarhus University, Denmark.
Maja Holch
MH
Nielsen
Department of Molecular Biology and Genetics, Gustav Wieds Vej 10C, DK-8000 Aarhus C, Aarhus University, Denmark.
Rasmus Kock
RK
Flygaard
Department of Molecular Biology and Genetics, Gustav Wieds Vej 10C, DK-8000 Aarhus C, Aarhus University, Denmark.
Lasse Bohl
LB
Jenner
D022001:Focal Adhesions / Q000235:genetics; D006801:Humans; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics*; D011485:Protein Binding; D014176:Protein Biosynthesis; D011487:Protein Conformation; D000075370:Receptors for Activated C Kinase / Q000737:chemistry / Q000235:genetics*; D012269:Ribosomal Proteins / Q000235:genetics*; D012270:Ribosomes / Q000235:genetics*; D015398:Signal Transduction; D013329:Structure-Activity Relationship
D009363:Neoplasm Proteins; C419368:RACK1 protein, human; D000075370:Receptors for Activated C Kinase; D012269:Ribosomal Proteins
RACK1; Ribosome; Structure; Translational control