Translation Initiation
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Translation Initiation
In molecular biology, initiation factors are proteins that bind to the small subunit of the ribosome during the initiation of translation, a part of protein biosynthesis. Initiation factors can interact with repressors to slow down or prevent translation. They have the ability to interact with activators to help them start or increase the rate of translation. In bacteria, they are simply called IFs (i.e.., IF1, IF2, & IF3) and in eukaryotes they are known as eIFs (i.e.., eIF1, eIF2, eIF3). Translation initiation is sometimes described as three step process which initiation factors help to carry out. First, the tRNA carrying a methionine amino acid binds to the small subunit of ribosome, then binds to the mRNA, and finally joins together with the large subunit of ribosome. The initiation factors that help with this process each have different roles and structures. Types The initiation factors are divided into three major groups by taxonomic domains. There are some homologies sh ...
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Molecular Biology
Molecular biology is a branch of biology that seeks to understand the molecule, molecular basis of biological activity in and between Cell (biology), cells, including biomolecule, biomolecular synthesis, modification, mechanisms, and interactions. Though cells and other microscopic structures had been observed in living organisms as early as the 18th century, a detailed understanding of the mechanisms and interactions governing their behavior did not emerge until the 20th century, when technologies used in physics and chemistry had advanced sufficiently to permit their application in the biological sciences. The term 'molecular biology' was first used in 1945 by the English physicist William Astbury, who described it as an approach focused on discerning the underpinnings of biological phenomena—i.e. uncovering the physical and chemical structures and properties of biological molecules, as well as their interactions with other molecules and how these interactions explain observ ...
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Prokaryotic Initiation Factors
A bacterial initiation factor (IF) is a protein that stabilizes the initiation complex for polypeptide translation. Translation initiation is essential to protein synthesis and regulates mRNA translation fidelity and efficiency in bacteria. The 30S ribosomal subunit, initiator tRNA, and mRNA form an initiation complex for elongation. This complex process requires three essential protein factors in bacteria – IF1, IF2, and IF3. These factors bind to the 30S subunit and promote correct initiation codon selection on the mRNA. IF1, the smallest factor at 8.2 kDa, blocks elongator tRNA binding at the A-site. IF2 is the major component that transports initiator tRNA to the P-site. IF3 checks P-site codon-anticodon pairing and rejects incorrect initiation complexes. The orderly mechanism of initiation starts with IF3 attaching to the 30S subunit and changing its shape. IF1 joins next, followed by mRNA binding, and starts codon-P-site interaction. IF2 enters with the initiator tRNA and p ...
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OB-fold
In molecular biology, the OB-fold (oligonucleotide/oligosaccharide-binding fold) is a small protein structural motif observed in different proteins that bind oligonucleotides or oligosaccharides. It was originally identified in 1993 in four unrelated proteins: staphylococcal nuclease, anticodon binding domain of aspartyl-tRNA synthetase, and the B-subunits of heat-labile enterotoxin and verotoxin-1. Since then it has been found in multiple proteins many of which are involved in genome stability. This fold is often described as a Greek key motif. Structure The OB-fold consists of a five-stranded β-sheet coiled to form a closed β-barrel, capped by an α-helix located at one end and a binding cleft at the other. The α-helix packs against the bottom layer of residues, roughly perpendicular to the barrel axis. The β-sheet structure protrudes beyond this layer and packs around the sides of the helix. The binding specificities of each OB-fold depend on the different length, sequ ...
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Eukaryotic Initiation Factor
Eukaryotic initiation factors (eIFs) are proteins or protein complexes involved in the initiation phase of eukaryotic translation. These proteins help stabilize the formation of ribosomal preinitiation complexes around the start codon and are an important input for post-transcription gene regulation. Several initiation factors form a complex with the small 40S ribosomal subunit and Met- tRNAiMet called the 43S preinitiation complex (43S PIC). Additional factors of the eIF4F complex (eIF4A, E, and G) recruit the 43S PIC to the five-prime cap structure of the mRNA, from which the 43S particle scans 5'-->3' along the mRNA to reach an AUG start codon. Recognition of the start codon by the Met-tRNAiMet promotes gated phosphate and eIF1 release to form the 48S preinitiation complex (48S PIC), followed by large 60S ribosomal subunit recruitment to form the 80S ribosome. There exist many more eukaryotic initiation factors than prokaryotic initiation factors, reflecting the gre ...
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EIF6
Eukaryotic translation initiation factor 6 (EIF6), also known as Integrin beta 4 binding protein (ITGB4BP), is a human gene. Hemidesmosomes are structures which link the basal lamina to the intermediate filament cytoskeleton. An important functional component of hemidesmosomes is the integrin beta-4 subunit (ITGB4), a protein containing two fibronectin type III domains. The protein encoded by this gene binds to the fibronectin type III domains of ITGB4 and may help link ITGB4 to the intermediate filament cytoskeleton. The encoded protein, which is insoluble and found both in the nucleus and in the cytoplasm, can function as a translation initiation factor and catalyzes the association of the 40S and 60S ribosomal subunits along with eIF5 bound to GTP. Multiple transcript variants encoding several different isoforms have been found for this gene. EIF6 plays important roles in Eukaryotic 80S ribosome formation, cell growth and gene expression. The 80S ribosome, which can separate ...
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EIF5A
Eukaryotic translation initiation factor 5A-1 is a protein that in humans is encoded by the ''EIF5A'' gene. It is the only known protein to contain the unusual amino acid hypusine 'N''ε-(4-amino-2-hydroxybutyl)-lysine which is synthesized on eIF5A at a specific lysine residue from the polyamine spermidine by two catalytic steps. EF-P is the bacterial homolog of eIF5A, which is modified post-translationally in a similar but distinct way. Both proteins are believed to catalyze peptide bond formation and help resolve ribosomal stalls, making them elongation factors despite the "initiation factor" name originally assigned. Faundes-Banka syndrome Germline deleterious heterozygous ''EIF5A'' variants cause Faundes-Banka syndrome. This rare human disorder is characterized by variable combinations of developmental delay, microcephaly Microcephaly (from Neo-Latin ''microcephalia'', from Ancient Greek μικρός ''mikrós'' "small" and κεφαλή ''kephalé'' "head") is a me ...
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Elongation Factor P
EF-P (elongation factor P) is an essential protein that in bacteria stimulates the formation of the first peptide bonds in protein synthesis. Studies show that EF-P prevents ribosomes from stalling during the synthesis of proteins containing consecutive prolines. EF-P binds to a site located between the binding site for the peptidyl tRNA ( P site) and the exiting tRNA ( E site). It spans both ribosomal subunits with its amino-terminal domain positioned adjacent to the aminoacyl acceptor stem and its carboxyl-terminal domain positioned next to the anticodon stem-loop of the P site-bound initiator tRNA. The EF-P protein shape and size is very similar to a tRNA and interacts with the ribosome via the exit “E” site on the 30S subunit and the peptidyl-transferase center (PTC) of the 50S subunit. EF-P is a translation aspect of an unknown function, therefore It probably functions indirectly by altering the affinity of the ribosome for aminoacyl-tRNA, thus increasing their reactivity ...
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Prokaryotic Initiation Factor-3
In molecular biology, translation initiation factor IF-3 (gene infC) is one of the three factors required for the initiation of protein biosynthesis in bacteria. IF-3 is thought to function as a fidelity factor during the assembly of the ternary initiation complex which consists of the 30S ribosomal subunit, the initiator tRNA and the messenger RNA. IF-3 is a basic protein that binds to the 30S ribosomal subunit. The chloroplast homolog enhances the poly( A, U, G)-dependent binding of the initiator tRNA to its ribosomal 30s subunits. IF1–IF3 may also perform ribosome recycling. IF3 is not universally found in all bacterial species. However, in ''E. coli'', it is required for the 30S subunit to bind to the initiation site in mRNA. In addition, it has several other jobs including the stabilization of free 30S subunits, enables 30S subunits to bind to mRNA and checks for accuracy against the first aminoacyl-tRNA. It also allows for rapid codon-anticodon pairing for the initiato ...
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SUI1
In molecular biology, the single-domain protein SUI1 is a translation initiation factor often found in the fungus, ''Saccharomyces cerevisiae'' (Baker's yeast) but it is also found in other eukaryotes and prokaryotes as well as archaea. It is otherwise known as Eukaryotic translation initiation factor 1 (eIF1) in eukaryotes or ''YciH'' in bacteria. Function SUI1 is a translation initiation factor that directs the ribosome to the translation start site, helped by eIF2 and the initiator Met-tRNAiMet. SUI1 ensures that translation initiation commences from the correct start codon (usually AUG), by stabilizing the pre-initiation complex around the start codon. SUI1 promotes a high initiation fidelity for the AUG codon, discriminating against non-AUG codons. In ''E. coli'' however, it seems that the SUI1 homolog ''YciH'' is an inhibitor of translation during stress instead. Structure The primary structure of the SUI1 protein is made up of 108 amino acids. The protein domain has ...
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EIF5B
Eukaryotic translation initiation factor 5B is a protein that in humans is encoded by the ''EIF5B'' gene. Accurate initiation of translation in eukaryotes is complex and requires many factors, some of which are composed of multiple subunits. The process is simpler in bacteria which have only three initiation factors (IF1, IF2, IF3). Two of these factors are conserved in eukaryotes: the homolog of IF1 is eIF1A and the homolog of IF2 is eIF5B. This gene encodes eIF5B. Factors eIF1A and eIF5B interact on the ribosome along with other initiation factors and GTP to position the initiation methionine tRNA on the start codon of the mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ... so that translation initiates accurately. References Further reading

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Prokaryotic Initiation Factor-2
Bacterial initiation factor-2 is a bacterial initiation factor. IF2 binds to an initiator tRNA and controls the entry of tRNA onto the ribosome. IF2, bound to GTP, binds to the 30S The prokaryotic small ribosomal subunit, or 30Svedberg, S subunit, is the smaller subunit of the 70S ribosome found in prokaryotes. It is a complex of the 16S ribosomal RNA (rRNA) and 19 proteins. This complex is implicated in the binding of tr ... P site. After associating with the 30S subunit, fMet-tRNAf binds to the IF2 then IF2 transfers the tRNA into the partial P site. When the 50S subunit joins, it hydrolyzes GTP to GDP and Pi, causing a conformational change in the IF2 that causes IF2 to release and allow the 70S ribosome to form. Human mitochondria use a nuclear-encoded homolog, MTIF2, for translation initiation. References {{GTPases Protein biosynthesis Gene expression ...
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EIF1A
Eukaryotic translation initiation factor 1A, X-chromosomal (eIF1A) is a protein that in humans is encoded by the ''EIF1AX'' gene. This gene encodes an essential eukaryotic translation initiation factor. The protein is a component of the 43S pre-initiation complex (PIC), which mediates the recruitment of the small 40S ribosomal subunit to the 5' cap of messenger RNAs. Function eIF1A is a small protein (17 kDa in budding yeast) and a component of the 43S preinitiation complexes (PIC). eIF1A binds near the ribosomal A-site, in a manner similar to the functionally related bacterial counterpart IF1. Clinical significance Mutations in this gene have been recurrently seen associated to cases of uveal melanoma with disomy 3. eIF1A is mutated in thyroid cancers. Interactions EIF1AX has been shown to interact with IPO13 Importin-13 is a protein encoded by the IPO13 gene in humans. Importin-13 is a member of the importin-β family of nuclear transport receptors (NTRs) and was f ...
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