Statistical and functional analyses of viral and cellular proteins with N-terminal amphipathic alpha-helices with large hydrophobic moments: importance to macromolecular recognition and organelle targeting.

A total of 1,911 proteins with N-terminal methionyl residues were computer screened for potential N-terminal alpha-helices with strong amphipathic character. By the criteria of D. Eisenberg (Annu. Rev. Biochem. 53:595-623, 1984), only 3.5% of nonplastid, nonviral proteins exhibited potential N-terminal alpha-helices, 18 residues in length, with hydrophobic moment values per amino acyl residue ([muH]) in excess of 0.4. By contrast, 10% of viral proteins exhibited corresponding [muH] values in excess of 0.4. Of these viral proteins with known functions, 55% were found to interact functionally with nucleic acids, 30% were membrane-interacting proteins or their precursors, and 15% were structural proteins, primarily concerned with host cell interactions. These observations suggest that N-terminal amphipathic alpha-helices of viral proteins may (i) function in nucleic acid binding, (ii) facilitate membrane insertion, and (iii) promote host cell interactions. Analyses of potential amphipathic N-terminal alpha-helices of cellular proteins are also reported, and their significance to organellar or envelope targeting is discussed.