DIFFERENTIAL PROCESSING OF HUMAN AND RAT E1ALPHA-PRECURSORS OF THE BRANCHED-CHAIN ALPHA-KETO ACID DEHYDROGENASE COMPLEX CAUSED BY AN N-TERMINAL PROLINE IN THE RAT SEQUENCE

The N-terminal sequences of the E1 alpha, E1 beta and E2 subunits of t he human branched-chain alpha-keto acid dehydrogenase complex have bee n determined by microsequencing. The N-termini of human E1 beta and E2 subunits (Val and Gly, respectively) are identical to those of the co rresponding rat and bovine subunits. However, the N-terminus of the hu man E1 alpha subunit (Ser) is identical to bovine, but differs from th e rat E1 alpha (Phe) subunit. Comparison of the N-terminal sequences o f human and rat E1 alpha subunits shows that the serine residue at the fl position in the human sequence is replaced by a proline residue in the rat sequence. The presence of the proline residue apparently caus es a 5'-shift by one residue in the cleavage site by the mitochondrial processing peptidase in the rat sequence, when compared to the human sequence. The results provide evidence that the mitochondrial processi ng peptidase cannot cleave an X-Pro bond, similar to trypsin, chymotry psin and microsomal signal peptidases.