title: Comprehensive analysis of all triple helical repeats in beta-spectrins reveals patterns of selective evolutionary conservation.
abstract: The spectrin superfamily (spectrin, alpha-actinin, utrophin and dystrophin) has in common a triple helical repeating unit of ~106 amino acid residues. In spectrin, alpha and beta chains contain multiple copies of this repeat. beta-spectrin chains contain the majority of binding activities in spectrin and are essential for animal life. Canonical beta-spectrins have 17 repeats; beta-heavy spectrins have 30. Here, the repeats of five human beta-spectrins, plus beta-spectrins from several other vertebrates and invertebrates, have been analysed. Repeats 1, 2, 14 and 17 in canonical beta are highly conserved between invertebrates and vertebrates, and repeat 8 in some isoforms. This is consistent with conservation of critical functions, since repeats 1, 2 and 17 bind alpha-spectrin. Repeats 1 of beta-spectrins are not always detected by SMART or Pfam tools. A profile hidden Markov model of beta-spectrin repeat 1 detects alpha-actinins, but not utrophin or dystrophin. Novel examples of repeat 1 were detected in the spectraplakins MACF1, BPAG1 and plectin close to the actin-binding domain. Ankyrin binds to the C-terminal portion of repeat 14; the high conservation of this entire repeat may point to additional, undiscovered ligand-binding activities. This analysis indicates that the basic triple helical repeat pattern was adapted early in the evolution of the spectrin superfamily to encompass essential binding activities, which characterise individual repeats in proteins extant today.
authors.affiliation: Randall Centre for Molecular Mechanisms of Cell Function, King's College London, Guy's Campus, UK. A.J.Baines@ukc.ac.uk
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Baines
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D017124:Conserved Sequence; D019143:Evolution, Molecular; D006801:Humans; D007448:Invertebrates / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D010802:Phylogeny; D017433:Protein Structure, Secondary; D020449:Repetitive Sequences, Amino Acid; D017386:Sequence Homology, Amino Acid; D013049:Spectrin / Q000737:chemistry* / Q000235:genetics*; D014714:Vertebrates / Q000235:genetics
chemical_list: D013049:Spectrin