Cleavage-site motifs in mitochondrial targeting peptides Ylva Gavel and Gunnar von Heijnel>2

2To whom correspondence should be addressed Although mitochondria] targeting peptides lack a common consensus sequence, a certain bias in the positional distribution of amino acids has recently been found. These patterns seem to be associated with cleavage of the precursor proteins by matrix processing proteases. We have extended the previous studies and found new sequence motifs that are conserved within subgroups of mitochondria] targeting peptides. These motifs have certain common themes, indicating that they are associated with cleavage by one single protease. Two of the conserved patterns have a high predictive value, but even for sequences that do not possess these patterns, a fairly accurate prediction of the cleavage site is shown to be possible. We also suggest that a well-conserved RXY1(S/A) pattern may be used to engineer efficiently recognized cleavage sites into uncleaved or artificial mito-chondrial targeting peptides. Key words: cleavage site/matrix processing proteases/mito chondrial targeting peptides/precursor proteins/sequence motif