Related Experiment Video
Updated: Aug 27, 2025
08:47
Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells
Published on: May 1, 2020
3.2K
Regulation of the interactions between human eIF5 and eIF1A by the CK2 kinase
Nathan Gamble1, Eleanor Elise Paul1, Bibin Anand1
1Department of Physiology & Biophysics, Boston University School of Medicine, 700 Albany St. W336, Boston, MA, 02118, USA.
Current Research in Structural Biology
|September 27, 2022
Summary
Eukaryotic translation factor 5 (eIF5) interacts with eIF1A via a new interface, enhanced by CK2 phosphorylation. This interaction is crucial for regulating protein synthesis and cell proliferation.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Eukaryotic translation initiation involves complex, dynamic interactions within the preinitiation complex (PIC).
- eIF5 acts as a GTPase-activating protein for eIF2 and plays a key role in PIC assembly and remodeling.
- Previous studies identified interactions between eIF5 C-terminal domain (CTD) and eIF1A N-terminal tail.
Purpose of the Study:
- To identify and characterize new interaction interfaces between eIF5 and eIF1A.
- To investigate the role of intramolecular dynamics in the eIF5-eIF1A interaction.
- To elucidate the impact of CK2 phosphorylation on eIF5-eIF1A binding and its implications for protein synthesis.
Main Methods:
- Biochemical assays to map protein-protein interaction interfaces.
- Structural analysis of protein domains involved in binding.
- Investigating the effects of post-translational modifications (phosphorylation) on protein interactions.
Main Results:
- A novel contact interface between eIF5-CTD and the oligonucleotide/oligosaccharide-binding (OB) domain of eIF1A was identified.
- Intramolecular dynamics within both eIF5 and eIF1A modulate their interaction.
- CK2 phosphorylation of eIF5 significantly increases its affinity for eIF1A.
Conclusions:
- The newly identified interface contributes to the overall affinity between eIF5 and eIF1A.
- CK2-mediated phosphorylation of eIF5 enhances its interaction with eIF1A, impacting translation regulation.
- These findings provide new insights into how CK2 stimulates protein synthesis and cell proliferation.
Related Concept Videos
02:34Inhibition of Cdk Activity
4.9K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.9K
02:39Positive Regulator Molecules
5.6K
Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
5.6K
01:16Calmodulin-dependent Signaling
5.2K
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
5.2K
01:31Regulation of the Unfolded Protein Response
2.5K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.5K
02:15M-Cdk Drives Transition Into Mitosis
5.7K
Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
5.7K
01:22PI3K/mTOR/AKT Signaling Pathway
3.8K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.8K