Regulation by heme of mitochondrial protein transport through a conserved amino acid motif.
A conserved motif, termed the heme regulatory motif (HRM), was identified in the presequences of the erythroid delta-aminolevulinate synthase precursors and was shown to be involved in hemin inhibition of transport of these proteins into mouse mitochondria in vitro. When the HRM was inserted into the presequence of the ornithine transcarbamoylase precursor, a normally unregulated mitochondrial protein, it conferred hemin inhibition on the transport of the chimeric protein. The conserved cysteine within the HRM was shown by site-directed mutagenesis to be required for hemin inhibition.
Lathrop
J T
JT
Department of Biology, University of Virginia, Charlottesville 22901.
Timko
M P
MP
D000624:5-Aminolevulinate Synthetase / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002645:Chickens; D004792:Enzyme Precursors / Q000378:metabolism*; D004912:Erythrocytes / Q000201:enzymology*; D006418:Heme / Q000494:pharmacology*; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008811:Mice, Inbred DBA; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D012045:Regulatory Sequences, Nucleic Acid; D017386:Sequence Homology, Amino Acid
D004792:Enzyme Precursors; D006418:Heme; D000624:5-Aminolevulinate Synthetase