The presequence of rat liver aldehyde dehydrogenase requires the presence of an alpha-helix at its N-terminal region which is stabilized by the helix at its C termini.
Previous nuclear magnetic resonance data showed that the conformation of the signal peptide of rat liver mitochondrial aldehyde dehydrogenase in a micelle environment contained a N-helix and a C-helix which were separated by a flexible hinge region (Karslake, C., Piotto, M.E., Pak, Y.K., Weiner, H. and Gorenstein, D. (1990) Biochemistry 29, 9872-9878). Deletion of either helix from the presequence caused complete loss of the precursor import. Switching the positions of the two helices had little effect on import but decreased processing efficiency. Import was not affected by replacing the C-helix with the N-terminal helix of the presequence of cytochrome c oxidase subunit IV, however, it was decreased by replacing the C-helix with the C-terminal random coil of the oxidase's presequence. Circular dichroism studies on the synthesized signal peptides indicated that a helix in the C-segment of aldehyde dehydrogenase signal peptide was needed to stabilize the N-helix. It is concluded that a stable helix in the N-terminal region is necessary for a functional mitochondrial presequence. This helix could be obtained from its own sequence, or from the interaction with other portions of the presequence.
Department of Biochemistry, Purdue University, West Lafayette, Indiana 47907-1153.
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Weiner
D000444:Aldehyde Dehydrogenase / Q000737:chemistry* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001692:Biological Transport; D004247:DNA; D003576:Electron Transport Complex IV / Q000737:chemistry; D004792:Enzyme Precursors / Q000737:chemistry / Q000378:metabolism; D008930:Mitochondria, Liver / Q000201:enzymology*; D008969:Molecular Sequence Data; D011487:Protein Conformation; D021382:Protein Sorting Signals / Q000737:chemistry* / Q000378:metabolism; D051381:Rats
D004792:Enzyme Precursors; D021382:Protein Sorting Signals; D004247:DNA; D000444:Aldehyde Dehydrogenase; D003576:Electron Transport Complex IV