start codon
Summary
The start codon is the mRNA sequence (usually AUG) that initiates protein synthesis and codes for methionine (or N-formylmethionine in prokaryotes). It sets the reading frame for translation, determining how subsequent codons are grouped and read.
Detail
During translation initiation, the small ribosomal subunit, along with initiator tRNA (charged with methionine in eukaryotes or N-formylmethionine, fMet, in prokaryotes/mitochondria), scans the mRNA to locate the start codon AUG. In eukaryotes, this typically occurs via cap-dependent scanning from the 5' cap, with the Kozak consensus sequence (GCCRCCAUGG) enhancing recognition efficiency. In prokaryotes, the Shine-Dalgarno sequence upstream of AUG base-pairs with 16S rRNA to position the ribosome correctly. Once the start codon is identified, the large ribosomal subunit joins to form the complete 80S (eukaryotic) or 70S (prokaryotic) ribosome, and elongation begins. The start codon establishes the reading frame—critical because a shift in this frame (as in frameshift mutations) alters the downstream codon groupings and typically produces a nonfunctional or truncated protein. Clinically relevant: mutations affecting the start codon (loss of AUG) can prevent translation initiation entirely, leading to complete loss of a functional protein product, relevant in conditions like certain hemoglobinopathies. Antibiotics such as aminoglycosides can interfere with initiation complex formation, contributing to bacterial protein synthesis inhibition.
Sources
- First Aid for the USMLE Step 1
- Molecular Biology of the Cell (Alberts et al.)
- Lippincott's Illustrated Reviews: Biochemistry
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