Patterns that define the four domains conserved in known and novel isoforms of the protein import receptor Tom20.
Tom20 is the master receptor for protein import into mitochondria. Analysis of motifs present in Tom20 sequences from fungi and animals found several highly conserved regions, including features of the transmembrane segment, the ligand-binding domain and functionally important flexible segments at the N terminus and the C terminus of the protein. Hidden Markov model searches of genome sequence data revealed novel isoforms of Tom20 in vertebrate and invertebrate animals. A three-dimensional comparative model of the novel type I Tom20, based on the structurally characterized type II isoform, shows important differences in the amino acid residues lining the ligand-binding groove, where the type I protein from animals is more similar to the fungal form of Tom20. Given that the two receptor types from mouse interact with the same set of precursor protein substrates, comparative analysis of the substrate-binding site provides unique insight into the mechanism of substrate recognition. No Tom20-related protein was found in genome sequence data from plants or protozoans, suggesting the receptor Tom20 evolved after the split of animals and fungi from the main lineage of eukaryotes.
Likić
Vladimir A
VA
Russell Grimwade School of Biochemistry and Molecular Biology, University of Melbourne, Melbourne 3010, Australia.
Perry
Andrew
A
Hulett
Joanne
J
Derby
Merran
M
Traven
Ana
A
Waller
Ross F
RF
Keeling
Patrick J
PJ
Koehler
Carla M
CM
Curran
Sean P
SP
Gooley
Paul R
PR
Lithgow
Trevor
T
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019143:Evolution, Molecular; D006801:Humans; D008390:Markov Chains; D033681:Mitochondrial Membrane Transport Proteins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism; D010802:Phylogeny; D011487:Protein Conformation; D020033:Protein Isoforms / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
D033681:Mitochondrial Membrane Transport Proteins; D010455:Peptides; D020033:Protein Isoforms; D018160:Receptors, Cytoplasmic and Nuclear; D029701:Saccharomyces cerevisiae Proteins; C489350:TOM20 protein, S cerevisiae