Molecular evolution of ankyrin: gain of function in vertebrates by acquisition of an obscurin/titin-binding-related domain.
Ankyrins form a family of modular adaptor proteins that link between integral membrane proteins and the cytoskeleton. They evolved within the Metazoa as an adaptation for organizing membrane microstructure and directing membrane traffic. Molecular cloning has identified one Caenorhabditis elegans (unc-44), two Drosophila (Dank1, Dank2), and three mammalian (Ank1, Ank2, Ank3) genes. We have previously identified a 76-amino acid (aa) alternatively spliced sequence that is present in muscle polypeptides encoded by the rat Ank3 gene. A closely related sequence in a muscle Ank1 product binds the cytoskeletal muscle proteins obscurin and titin. This obscurin/titin-binding-related domain (OTBD) contains repeated modules of 18 aa: three are encoded by Ank1 and Ank2, two by Ank3; this pattern is conserved throughout vertebrate ankyrin genes. The C. elegans ankyrin, UNC-44, contains one 18-aa module as does the ankyrin gene in the urochordate Ciona intestinalis, but the insect ankyrins contain none. Our data indicate that an ancestral ankyrin acquired an 18-aa module which was preserved in the Ecdysozoa/deuterostome divide, but it was subsequently lost from arthropods. Successive duplications of the module led to a gain of function in vertebrates as it acquired obscurin/titin-binding activity. We suggest that the OTBD represents an adaptation of the cytoskeleton that confers muscle cells with resilience to the forces associated with vertebrate life.
Hopitzan
Alexander A
AA
Institut Jacques Monod/CNRS/Universités Paris VI et VII, Paris, France.
Baines
Anthony J
AJ
Kordeli
Ekaterini
E
D000595:Amino Acid Sequence; D000818:Animals; D017487:Ankyrins / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D019295:Computational Biology; D064211:Connectin; D017124:Conserved Sequence / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D019143:Evolution, Molecular; D016013:Likelihood Functions; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000378:metabolism; D010802:Phylogeny; D011494:Protein Kinases / Q000378:metabolism; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D014714:Vertebrates / Q000235:genetics*
D017487:Ankyrins; D064211:Connectin; D003598:Cytoskeletal Proteins; D009124:Muscle Proteins; D011494:Protein Kinases