Using Hidden Markov Models to Discover New Protein Transport Machines

Protein import and export pathways are driven by protein translocases, often comprised of multiple subunits, and usually conserved across a range of organisms. Protein import into mitochondria is fundamental to eukaryotic organisms and is initiated when substrate proteins are translocated across the mitochondrial outer membrane by the TOM complex. The essential subunit of this complex is a protein called Tom40, which is probably a β-barrel in structure and serves as the translocation pore. We describe a hidden Markov model search designed to find the Tom40 sequence in the amoeba Entamoeba histolytica . This organism has a highly reduced “mitosome”, an organelle whose relationship to mitochondria has been the subject of controversy. The Tom40 sequence could not be found with BLAST-based searches, but a hidden Markov model search identified a likely candidate to form the protein import pore in the outer mitosomal membrane in E. histolytica .