GO:0061770 translation elongation factor binding: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0061770 (translation elongation factor binding) is a molecular function defined as binding to a translation elongation factor, any polypeptide factor involved in peptide elongation in ribosome-mediated translation.
• Key elongation factors include eEF3, eEF2, EF-Tu, and EF-P, which bind the ribosome or ribosomal subunits to drive tRNA translocation and peptide bond formation.
• Elongation factor binding is tightly regulated; for example, GCN1 engages GCN2 on stalled ribosomes to signal amino acid stress and promote degradation of translation factors.
• Dysregulation of elongation factor binding is linked to cancer, neurodegeneration, and ribosomopathies, making it a target for therapeutic intervention.
• CRISPR knockout, point mutation, knock-in, and overexpression models enable precise dissection of elongation factor binding in human cells.
• EDITGENE provides end-to-end CRISPR services, including library screening and bioinformatics, to accelerate research on translation elongation factor binding.
Description
Translation elongation factor binding (GO:0061770) is a molecular function that mediates the interaction between translation elongation factors and their binding partners, typically the ribosome or ribosomal subunits, during the elongation phase of protein synthesis. This function is essential for the accurate and efficient addition of amino acids to the growing polypeptide chain. Elongation factors such as eEF3 in yeast and EF-Tu in bacteria bind to the ribosome to facilitate tRNA translocation and maintain translational fidelity. In eukaryotes, eEF2 catalyzes the translocation step, and its binding to the ribosome is a critical point of regulation. The importance of this term extends beyond basic translation, as elongation factor binding is implicated in cellular stress responses, including the amino acid response pathway mediated by GCN1 and GCN2. Researchers studying translation regulation, antibiotic development, and disease mechanisms rely on understanding the molecular details of elongation factor binding.
translation elongation factor binding At A Glance
| GO ID | GO:0061770 |
|---|---|
| GO term | translation elongation factor binding |
| Ontology | molecular_function |
| Synonym | none |
| Major function | Binding to translation elongation factors during peptide elongation |
| Related factors | eEF3, eEF2, EF-Tu, EF-P, GCN1 |
| Associated processes | Translation elongation, tRNA translocation, stress response |
| Disease relevance | Cancer, neurodegeneration, ribosomopathies |
What Is GO:0061770?
According to the Gene Ontology, GO:0061770 (translation elongation factor binding) is defined as binding to a translation elongation factor, any polypeptide factor involved in peptide elongation in ribosome-mediated translation. In other words, it describes the molecular interaction between a protein and an elongation factor that participates in the elongation cycle of protein synthesis.
Why Is translation elongation factor binding Important in Cell Biology?
Translation elongation factor binding is a central molecular function that ensures the ribosome efficiently and accurately synthesizes proteins. Disruptions in this binding can lead to translational errors, stalled ribosomes, and activation of stress pathways such as the amino acid response. Moreover, elongation factors are targets of natural products and antibiotics, underscoring their therapeutic potential. Understanding the structural and regulatory aspects of elongation factor binding is therefore critical for basic biology and drug discovery.
• Essential for protein synthesis and cell viability.
• Regulates translation speed and fidelity.
• Involved in the amino acid response pathway via GCN1/GCN2.
• Targeted by antibiotics and natural products like melleolides.
• Implicated in cancer through dysregulated translation.
• Linked to neurodegeneration via impaired translational control.
• Plays a role in ribosomopathies and developmental disorders.
• Enables mechanistic studies using CRISPR screens and Ribo-seq.
• Facilitates structural biology of translation complexes.
• Provides biomarkers for stress and disease states.
What Happens During translation elongation factor binding?
Binding of eEF3 to the Ribosome
In simple terms: eEF3 attaches to the ribosome to help move tRNA molecules during protein building.
In yeast, translation elongation factor eEF3 binds to the ribosome and promotes late stages of tRNA translocation, facilitating the release of deacylated tRNA from the E site. This binding is essential for efficient elongation and is a key step in the elongation cycle.
EF-Tu Binding in Bacteria
In simple terms: EF-Tu carries aminoacyl-tRNA to the ribosome and binds there to deliver the correct amino acid.
In Mycobacterium tuberculosis, EF-Tu forms complexes with the ribosome and tRNA, and structural insights reveal how its binding ensures accurate codon recognition and peptide bond formation. This binding is a target for antibacterial drugs.
eEF2 Catalyzes Reverse Translocation
In simple terms: eEF2 can also move the ribosome backward under certain conditions, showing its versatile binding.
Eukaryotic translation elongation factor 2 (eEF2) binds the ribosome and catalyzes reverse translocation, a process that can rescue stalled ribosomes and maintain translational homeostasis. This reverse activity highlights the dynamic nature of elongation factor binding.
EF-P and Ribosome Stalling
In simple terms: EF-P binds to the ribosome to help it continue when it gets stuck on certain amino acid sequences.
Elongation factor P (EF-P) binds to the ribosome and alleviates stalling on proline-rich sequences, thereby controlling translation elongation. Its binding is also important for maintaining transcription-translation coupling.
GCN1-Mediated Factor Degradation
In simple terms: GCN1 binds to stalled ribosomes and recruits machinery to degrade translation factors, signaling stress.
The E3 ligase network engages GCN1 to promote the degradation of translation factors on stalled ribosomes. GCN1 couples GCN2 to the ribosomal state to initiate amino acid response signaling, linking elongation factor binding to stress adaptation.
Key Genes Involved in GO:0061770 translation elongation factor binding
The following genes encode proteins that bind translation elongation factors or are themselves elongation factors, playing critical roles in translation elongation and its regulation.
| Gene | Major Role | Research Relevance |
|---|---|---|
| eEF3 (YEF3) | Binds ribosome to promote tRNA translocation in yeast | Model for elongation factor binding studies |
| eEF2 (EEF2) | Catalyzes ribosomal translocation and reverse translocation | Target in cancer and neurodegeneration |
| EF-Tu (tuf) | Delivers aminoacyl-tRNA to bacterial ribosome | Antibiotic target; structural studies |
| EF-P (efp) | Alleviates ribosome stalling on proline-rich sequences | Translation fidelity and stress response |
| GCN1 (GCN1) | Binds stalled ribosomes; activates GCN2 | Amino acid response signaling |
| GCN2 (EIF2AK4) | Kinase activated by GCN1 upon stress | Integrated stress response |
| RPL (ribosomal proteins) | Components of ribosome that interact with factors | Structural and functional studies |
| RACK1 (RACK1) | Ribosome-associated scaffold protein | Modulates translation and stress |
| eIF5A (EIF5A) | Elongation factor with hypusine modification | Translation elongation and cancer |
| EF-1A (EEF1A1) | Delivers aminoacyl-tRNA to eukaryotic ribosome | Cancer and translation regulation |
| EF-G (fusA) | Bacterial translocation factor | Antibiotic target |
| eEF1B (EEF1B2) | Guannine nucleotide exchange factor for eEF1A | Translation elongation |
| eEF2K (EEF2K) | Kinase that phosphorylates eEF2 | Regulation of elongation |
| Melleolide targets (eEF2) | Natural product binds eEF2 | Antifungal drug discovery |
| GCN20 (GCN20) | Part of GCN1 complex | Stress response |
| ABC50 (ABCF1) | Ribosome-associated factor | Translation initiation and elongation |
| eIF2α (EIF2S1) | Translation initiation factor | Integrated stress response |
How Is translation elongation factor binding Regulated?
Translation elongation factor binding is regulated at multiple levels. The GCN1-GCN2 pathway senses amino acid starvation and stalled ribosomes, leading to phosphorylation of eIF2α and inhibition of global translation while activating stress-responsive genes. Additionally, eEF2 activity is controlled by eEF2K-mediated phosphorylation, which modulates its binding to the ribosome. Natural products such as melleolides can directly inhibit eEF2 binding, affecting fungal translation. These regulatory mechanisms ensure that elongation factor binding is dynamically adjusted to cellular conditions.
translation elongation factor binding and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| EEF2 | Cancer, neurodegeneration | Knockout and point mutation in cancer cell lines |
| GCN1 | Amino acid stress, cancer | Knockout in HEK293T for stress response |
| EF-P (efp) | Bacterial virulence | Knockout in E. coli and infection models |
| EF-Tu (tuf) | Tuberculosis | Knockout in M. tuberculosis |
| eEF3 (YEF3) | Fungal growth | Knockout in S. cerevisiae |
Cancer
Dysregulated translation elongation contributes to oncogenesis. Overexpression or altered binding of eEF2 and eEF1A has been observed in various cancers, promoting tumor growth and survival. Targeting elongation factor binding is a potential therapeutic strategy.
Neurodegeneration
Impaired translational control and elongation factor binding are implicated in neurodegenerative diseases. For example, eEF2 dysregulation affects synaptic plasticity and neuronal survival. Stress pathways involving GCN1/GCN2 also play roles in neurodegeneration.
Ribosomopathies
Mutations in ribosomal proteins or elongation factors can lead to ribosomopathies, such as Diamond-Blackfan anemia. Defects in elongation factor binding disrupt protein synthesis and cellular homeostasis.
Infectious Diseases
Bacterial elongation factors like EF-Tu are targets for antibiotics. Understanding their binding mechanisms aids in developing new antimicrobials. Fungal eEF2 is targeted by melleolides, offering antifungal strategies.
From translation elongation factor binding-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of eEF2 binding affect translation? | CRISPR knockout of EEF2 in HeLa cells |
| Does a point mutation in EF-Tu alter antibiotic resistance? | Point mutation knock-in in M. tuberculosis |
| Can tagged eEF3 be used to pull down ribosomes? | Knock-in of FLAG-tag at YEF3 locus in yeast |
| Does overexpression of eEF1A promote cancer? | Overexpression in MCF7 cells |
| What genes regulate elongation factor binding? | Genome-wide CRISPR library screening |
| How does GCN1 binding change under stress? | Knockout of GCN1 in HEK293T followed by Ribo-seq |
How to Study the translation elongation factor binding Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Ribo-seq | Ribosome occupancy and translation efficiency | Studying elongation pausing |
| Co-IP/MS | Protein-protein interactions | Identifying binding partners |
| Cryo-EM | 3D structure of complexes | Visualizing factor-ribosome binding |
| CRISPR screen | Gene essentiality and modifiers | Discovering regulators |
| Western blot | Protein expression and phosphorylation | Validating knockout/overexpression |
| Polysome profiling | Global translation status | Assessing elongation defects |
| In vitro translation | Direct effect on peptide synthesis | Testing factor activity |
Ribosome Profiling (Ribo-seq)
Ribo-seq provides a snapshot of ribosome positions on mRNA, revealing how elongation factor binding affects translation speed and pausing. It is widely used to study the impact of mutations in elongation factors.
Proteomics and Co-immunoprecipitation
Co-IP followed by mass spectrometry can identify proteins that bind to elongation factors, uncovering interaction networks. This method is useful for discovering novel binding partners.
Structural Biology (Cryo-EM, X-ray)
Cryo-EM and X-ray crystallography resolve the atomic details of elongation factor-ribosome complexes, as shown for EF-Tu and eEF3. These techniques guide drug design.
CRISPR Screening
Genome-wide CRISPR knockout screens can identify genes that modulate elongation factor binding and translation. This approach is powerful for discovering regulators.
How CRISPR Can Be Used to Study GO:0061770 translation elongation factor binding
Knockout
CRISPR knockout of elongation factor genes (e.g., EEF2, GCN1) allows researchers to assess their essentiality and impact on translation. For example, GCN1 knockout abolishes amino acid response signaling.
Point Mutation
Introducing point mutations in elongation factor binding domains (e.g., EF-Tu) can reveal residues critical for ribosome interaction and antibiotic resistance.
Knock-in
Knock-in of epitope tags (e.g., FLAG, HA) at endogenous loci enables affinity purification and imaging of elongation factors in their native context.
Overexpression
Overexpression of elongation factors like eEF1A can model oncogenic translation and test drug sensitivity.
How EDITGENE Supports translation elongation factor binding Research
Researchers studying translation elongation factor binding-related genes often need to determine whether a candidate gene is causally involved in translation regulation, stress response, or disease. EDITGENE provides a comprehensive suite of CRISPR services to generate precisely engineered cell models, enabling functional validation and mechanistic studies.
Contact EDITGENE today to design your custom CRISPR model for translation elongation factor binding research.
Frequently Asked Questions About translation elongation factor binding
What is translation elongation factor binding?
It is the molecular function of binding to a translation elongation factor, which helps add amino acids to a growing protein chain during translation.
What genes are involved in translation elongation factor binding?
Key genes include EEF2, GCN1, EF-Tu (tuf), EF-P (efp), and eEF3 (YEF3), among others.
How is translation elongation factor binding regulated?
It is regulated by stress pathways like GCN1-GCN2 and phosphorylation of eEF2 by eEF2K.
What diseases are associated with translation elongation factor binding?
Cancer, neurodegeneration, ribosomopathies, and infectious diseases.
What methods study translation elongation factor binding?
Ribo-seq, co-immunoprecipitation, cryo-EM, and CRISPR screens are commonly used.
Can CRISPR be used to study translation elongation factor binding?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models enable precise functional studies.
What is the role of GCN1 in translation elongation factor binding?
GCN1 binds stalled ribosomes and activates GCN2, leading to degradation of translation factors and stress signaling.
How does eEF2 binding affect translation?
eEF2 catalyzes ribosomal translocation and can also promote reverse translocation, influencing translation dynamics.
What is EF-P and how does it bind?
EF-P is an elongation factor that binds the ribosome to alleviate stalling on proline-rich sequences.
Why is translation elongation factor binding important for drug discovery?
Elongation factors are targets of antibiotics and natural products, and their binding interfaces are potential drug targets.
Conclusion
Translation elongation factor binding (GO:0061770) is a fundamental molecular function that ensures efficient and accurate protein synthesis. Its dysregulation is linked to a wide range of diseases, from cancer to neurodegeneration. Advances in CRISPR technology and structural biology continue to unravel the complexities of this process, offering new opportunities for therapeutic intervention. EDITGENE stands ready to support your research with tailored CRISPR models and bioinformatics solutions.
References
- 1. Ranjan N et al.. 2021. Yeast translation elongation factor eEF3 promotes late stages of tRNA translocation.. EMBO J 40(6):e106449 PMID: 33555093
- 2. Dörfer M et al.. 2019. Melleolides impact fungal translation via elongation factor 2.. Org Biomol Chem 17(19):4906-4916 PMID: 31042251
- 3. Rajkovic A et al.. 2017. Elongation Factor P and the Control of Translation Elongation.. Annu Rev Microbiol 71:117-131 PMID: 28886684
- 4. Oltion K et al.. 2023. An E3 ligase network engages GCN1 to promote the degradation of translation factors on stalled ribosomes.. Cell 186(2):346-362.e17 PMID: 36638793
- 5. Elgamal S et al.. 2016. Maintenance of Transcription-Translation Coupling by Elongation Factor P.. mBio 7(5) PMID: 27624127
- 6. Zhan B et al.. 2022. Structural insights of the elongation factor EF-Tu complexes in protein translation of Mycobacterium tuberculosis.. Commun Biol 5(1):1052 PMID: 36192483
- 7. Zhou C et al.. 2025. GCN1 couples GCN2 to ribosomal state to initiate amino acid response pathway signaling.. Science 390(6768):eads8728 PMID: 41037622
- 8. Susorov D et al.. 2018. Eukaryotic translation elongation factor 2 (eEF2) catalyzes reverse translocation of the eukaryotic ribosome.. J Biol Chem 293(14):5220-5229 PMID: 29453282
