EEF1-Eukaryotic Translation Elongation Factor | Elisa - Clia - Antibody - Protein

Background:

The Eukaryotic Translation Elongation Factor 1 (EEF1), also known as eEF1, is a protein complex that plays a crucial role in protein synthesis, specifically in the elongation phase of translation. EEF1 is a heterotrimeric complex composed of three subunits: EEF1A, EEF1B, and EEF1G. EEF1A is the largest subunit of the complex and possesses GTPase activity. It binds GTP and interacts with both aa-tRNAs and the ribosome. EEF1B is a guanine nucleotide exchange factor (GEF) that catalyzes the exchange of GDP for GTP on EEF1A, thereby activating EEF1A for aa-tRNA binding. EEF1G is a structural component of the complex that interacts with EEF1A and EEF1B, facilitating their assembly into the functional EEF1 complex. EEF1 is responsible for delivering aminoacyl-tRNAs (aa-tRNAs) to the ribosome during translation elongation. It facilitates the binding of aa-tRNAs to the ribosomal A-site, where they are incorporated into the growing polypeptide chain. It has also GTPase Activity, EEF1 undergoes a cycle of GTP binding and hydrolysis, which is essential for its function in translation elongation. GTP binding promotes the formation of a complex between EEF1 and aa-tRNA, while GTP hydrolysis drives conformational changes in EEF1 that facilitate the release of aa-tRNA into the ribosomal A-site. EEF1 contributes to the fidelity of translation by ensuring the accurate selection and delivery of cognate aa-tRNAs to the ribosome. It discriminates against non-cognate or incorrectly charged tRNAs, thereby minimizing errors in protein synthesis.

Protein Structure:

• EEF1A: EEF1A is a GTP-binding protein that shuttles aminoacyl-tRNA to the ribosome. It has a highly conserved structure comprising three domains: a G-domain (GTPase domain), domain II, and domain III. The G-domain is responsible for binding and hydrolyzing GTP, which is crucial for its function.
• EEF1B Complex: The EEF1B complex is composed of multiple subunits (EEF1Bα, EEF1Bβ, and EEF1Bγ). EEF1Bα serves as a guanine nucleotide exchange factor (GEF) for EEF1A, facilitating the exchange of GDP for GTP. EEF1Bβ and EEF1Bγ assist in stabilizing the complex and enhancing its activity.

Classification and Subtypes:

EEF1 family members are classified based on their specific functions and sequence homology. Major subtypes include:

• EEF1A1 and EEF1A2: Isoforms of EEF1A that are differentially expressed in tissues; EEF1A1 is ubiquitously expressed, while EEF1A2 is primarily found in neurons and muscle tissues.
• EEF1Bα, EEF1Bβ, and EEF1Bγ: Subunits of the EEF1B complex that work together to regenerate the active GTP-bound form of EEF1A.

Function and Biological Significance:

• Translation Elongation: EEF1A binds to aminoacyl-tRNA and escorts it to the A site of the ribosome. Upon correct codon-anticodon pairing, EEF1A hydrolyzes GTP, releasing the aminoacyl-tRNA for incorporation into the growing polypeptide chain.
• Nucleotide Exchange: EEF1Bα catalyzes the exchange of GDP for GTP on EEF1A, reactivating it for another round of translation elongation.
• Protein Homeostasis: EEF1A interacts with various proteins involved in the cytoskeleton, signal transduction, and cellular stress responses, highlighting its role beyond translation.
• Cell Growth and Differentiation: EEF1 proteins are essential for cell proliferation and differentiation due to their fundamental role in protein synthesis.

Interactions:

• Ribosome: EEF1A directly interacts with the ribosome during the elongation phase of translation.
• Aminoacyl-tRNA: EEF1A forms a complex with aminoacyl-tRNA, ensuring the correct incorporation of amino acids.
• GTP and GDP: EEF1A functions as a GTPase, with its activity regulated by the binding and hydrolysis of GTP and GDP.
• EEF1B Complex: The EEF1B complex interacts with EEF1A to facilitate nucleotide exchange, maintaining the efficiency of translation elongation.

Clinical Issues:

• Cancer: Overexpression and mutations in EEF1A and EEF1B subunits have been linked to various cancers, including breast, lung, and ovarian cancers. These alterations can lead to uncontrolled cell growth and resistance to apoptosis.
• Neurological Disorders: EEF1A2 mutations are associated with neurodevelopmental disorders, such as intellectual disability and autism spectrum disorders, due to its critical role in neuronal function and development.
• Muscle Diseases: EEF1A2 dysregulation can contribute to muscle wasting and neurodegenerative conditions, given its high expression in muscle tissues.
• Viral Infections: EEF1 proteins are often hijacked by viruses to enhance viral protein synthesis, making them potential targets for antiviral therapies.

Summary:

Eukaryotic translation elongation factors (EEF1) are pivotal for the elongation phase of protein synthesis, ensuring the accurate and efficient addition of amino acids to polypeptide chains. Comprising essential proteins like EEF1A and the EEF1B complex, they interact with the ribosome, aminoacyl-tRNA, and various regulatory molecules. Beyond translation, EEF1 proteins are involved in diverse cellular processes, including cell growth, differentiation, and stress responses. Dysregulation of EEF1 family members is implicated in several diseases, notably cancer and neurological disorders, underscoring their importance in both normal cellular function and disease pathology.