On the predictive recognition of signal peptide sequences

Area of Science:

• Virology
• Molecular Biology
• Protein Biochemistry

Background:

• Herpes simplex virus (HSV) types 1 and 2 genomes contain unique regions with four uncharacterized genes: US2, US4, US5, and US7.
• Predicted amino acid sequences of these HSV genes exhibit hydrophobic N-termini, suggesting potential roles in membrane association.

Purpose of the Study:

• To investigate whether the hydrophobic N-termini of HSV US2, US4, US5, and US7 gene products function as signal sequences.
• To determine if these viral proteins are translated on membrane-bound ribosomes and subsequently inserted into or secreted from membranes.

Main Methods:

• Development of criteria to distinguish between proteins translated on membrane-bound versus free ribosomes, based on N-terminal region characteristics.
• Criteria included length and charge of the N-terminal region, length of the hydrophobic region, and hydrophobicity of the maximal hydrophobic region.
• Application of these criteria, particularly a two-dimensional plot combining hydrophobic parameters, to classify predicted HSV protein sequences.

Main Results:

• The developed criteria effectively distinguished membrane-translated proteins (96% accuracy).
• HSV gene products US4, US5, and US7 were convincingly classified as membrane-translated.
• The US2 gene product showed a less definitive classification but also indicated membrane association.

Conclusions:

• The gene products of HSV US4, US5, and US7 are likely previously unrecognized, virion membrane-inserted glycoproteins.
• The hydrophobic N-termini of these viral proteins probably act as signal sequences directing them to the membrane.