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Related Concept Videos

From DNA to Protein03:06

From DNA to Protein

The flow of genetic information in cells from DNA to mRNA to protein is described by the central dogma, which states that genes specify the sequence of mRNAs, which in turn specify the sequence of amino acids making up all proteins. The decoding of one molecule to another is performed by specific proteins and RNAs. Because the information stored in DNA is so central to cellular function, it makes intuitive sense that the cell would make mRNA copies of this information for protein synthesis...
Leaky Scanning02:28

Leaky Scanning

During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R stands for...
Improving Translational Accuracy02:07

Improving Translational Accuracy

Base complementarity between the three base pairs of mRNA codon and the tRNA anticodon is not a failsafe mechanism. Inaccuracies can range from a single mismatch to no correct base pairing at all. The free energy difference between the correct and nearly correct base pairs can be as small as 3 kcal/ mol. With complementarity being the only proofreading step, the estimated error frequency would be one wrong amino acid in every 100 amino acids incorporated. However, error frequencies observed in...
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tRNA Activation

Aminoacyl-tRNA synthetases are present in both eukaryotes and bacteria. Though eukaryotes have 20 different aminoacyl-tRNA synthetases to couple to 20 amino acids, many bacteria do not have genes for all of these aminoacyl-tRNA synthetases. Despite this, they still use all 20 amino acids to synthesize their proteins. For instance, some bacteria do not have the gene encoding the enzyme that couples glutamine with its partner tRNA. In these organisms, one enzyme adds glutamic acid to all of the...
Translation01:31

Translation

Lesson: Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
Translation01:31

Translation

Lesson: Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life

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Residue-specific Incorporation of Noncanonical Amino Acids into Model Proteins Using an Escherichia coli Cell-free Transcription-translation System
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Translationally optimal codons associate with structurally sensitive sites in proteins.

Tong Zhou1, Mason Weems, Claus O Wilke

  • 1Center for Computational Biology and Bioinformatics, The University of Texas at Austin, TX, USA.

Molecular Biology and Evolution
|April 8, 2009
PubMed
Summary

Selection favors high-fidelity codons at critical protein sites. This study found that translationally optimal codons correlate with buried residues and sites prone to disruptive mutations, supporting the protein misfolding hypothesis.

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Area of Science:

  • Genomics
  • Molecular Biology
  • Evolutionary Biology

Background:

  • The mistranslation-induced protein misfolding hypothesis posits that evolutionary selection favors high-fidelity codons at sites where translation errors cause structural disruption, leading to protein misfolding and aggregation.
  • Understanding the interplay between codon usage bias and protein structure is crucial for deciphering evolutionary pressures on gene expression.

Purpose of the Study:

  • To investigate the relationship between codon usage bias and protein structure in four model organisms (Escherichia coli, yeast, fly, and mouse).
  • To test the prediction that selection favors high-fidelity codons at structurally sensitive sites.

Main Methods:

  • Analysis of codon usage bias and protein structure data across the genomes of Escherichia coli, yeast, fly, and mouse.
  • Application of the Mantel-Haenszel procedure for categorical data and a novel association test for continuous variables.
  • Examination of results after excluding interdomain linkers to rule out confounding effects of solvent-accessible regions.

Main Results:

  • Translationally optimal codons were found to associate with buried amino acid residues.
  • Optimal codons also correlated with residues at sites where mutations cause significant changes in free energy (DeltaDeltaG).
  • This association was observed across most amino acids in at least one species and was independent of expression level, though it strengthened with increased expression.

Conclusions:

  • The findings support the mistranslation-induced protein misfolding hypothesis by demonstrating a link between codon optimality and protein structural stability.
  • Evolutionary selection appears to favor precise translation at critical protein sites to prevent misfolding and aggregation.
  • The study highlights the role of codon usage bias as a mechanism for maintaining protein integrity, particularly in highly expressed genes.