Membrane potential modulators: a thread of scarlet from plants to humans.
The preservation along evolution of specific core motifs in proteins of diverse functions and taxonomic origins pinpoints a possible developmental advantage at the structural level. Such a preservation was observed in a group of membrane potential modulators including plant gamma-thionins, scorpion toxins, insect and scorpion defensins, bee venom apamin and MCD peptide, snake sarafotoxins, and human endothelins. These substances are short polypeptides of various lengths and nonhomologous sequences that affect organisms of distant phyla. Despite the structural differences, comparative analysis reveals commonality at three levels: 1) effect on membrane potential; 2) a common cysteine-stabilized alpha-helical (CSH) motif; and 3) similar gene organization (except for insect defensins), i.e., an intron that splits a codon toward the end of the leader sequence. We thus propose that these modulators, divided into two groups differing in their CSH motif orientation, have either diverged from two independent ancestors or have evolved by gene diversification via exon shuffling and subsequent modifications. To enforce protein synthesis through the secretory pathway and enable disulfide bond formation and secretion, insertion sites downstream of preexisting leader sequences have been a prerequisite. What seems advantageous for evolution, may also be exploited in attempts to 'accelerate evolution' by protein design using the conserved CSH core as a suitable scaffold for reshaping molecular exteriors.
Froy
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Department of Plant Sciences, George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat-Aviv 69978, Tel Aviv, Israel.
Gurevitz
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D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides; D029681:Arabidopsis Proteins; D016232:Endothelins / Q000737:chemistry / Q000494:pharmacology; D019143:Evolution, Molecular; D008564:Membrane Potentials / Q000187:drug effects*; D008969:Molecular Sequence Data; D009498:Neurotoxins / Q000737:chemistry / Q000145:classification / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry / Q000145:classification / Q000494:pharmacology*; D010940:Plant Proteins / Q000737:chemistry / Q000494:pharmacology; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid; D014688:Venoms / Q000737:chemistry / Q000494:pharmacology
D023181:Antimicrobial Cationic Peptides; D029681:Arabidopsis Proteins; D016232:Endothelins; D009498:Neurotoxins; D010455:Peptides; D010940:Plant Proteins; C097482:THI2.1 protein, Arabidopsis; D014688:Venoms