Cotranslational protein folding and terminus hydrophobicity

Area of Science:

• Biochemistry
• Molecular Biology
• Computational Biology

Background:

• Protein folding is crucial for cellular function.
• Proteins can fold during synthesis (cotranslationally) or after release from the ribosome.
• The sequence and properties of amino acids influence protein folding pathways.

Purpose of the Study:

• To investigate the relationship between amino acid sequence properties and cotranslational folding success.
• To determine if N-terminus to C-terminus hydrophobicity differences impact cotranslational folding.
• To explore predictive measures for cotranslational folding efficiency.

Main Methods:

• Simulating hydrophobic-polar (HP) peptide folding on a square lattice.
• Analyzing real protein sequences using the Average Logarithmic Ratio (ALR) metric.
• Employing the SAINT program for cotranslational protein structure prediction.

Main Results:

• HP models showed better cotranslational folding with higher N-terminus hydrophobicity.
• Real proteins exhibited a correlation between ALR and N-C terminus hydrophobicity difference.
• SAINT predictions were more successful for proteins with a hydrophobic N-terminus and less hydrophobic C-terminus.

Conclusions:

• Cotranslational folding is promoted by a hydrophobic N-terminus and a less hydrophobic C-terminus.
• Hydrophobicity distribution along the polypeptide chain is a key factor in cotranslational folding.
• These findings offer insights into protein biogenesis and folding mechanisms.