Conserved structural and sequence elements implicated in the processing of gene-encoded circular proteins.
The cyclotides are the largest family of naturally occurring circular proteins. The mechanism by which the termini of these gene-encoded proteins are linked seamlessly with a peptide bond to form a circular backbone is unknown. Here we report cyclotide-encoding cDNA sequences from the plant Viola odorata and compare them with those from an evolutionarily distinct species, Oldenlandia affinis. Individual members of this multigene family encode one to three mature cyclotide domains. These domains are preceded by N-terminal repeat regions (NTRs) that are conserved within a plant species but not between species. We have structurally characterized peptides corresponding to these NTRs and show that, despite them having no sequence homology, they form a structurally conserved alpha-helical motif. This structural conservation suggests a vital role for the NTR in the in vivo folding, processing, or detoxification of cyclotide domains from the precursor protein.
Dutton
Julie L
JL
Institute for Molecular Bioscience, University of Queensland, Brisbane, Quuensland 4072, Australia.
Renda
Rosemary F
RF
Waine
Clement
C
Clark
Richard J
RJ
Daly
Norelle L
NL
Jennings
Cameron V
CV
Anderson
Marilyn A
MA
Craik
David J
DJ
D000595:Amino Acid Sequence; D000818:Animals; D019659:Asteraceae; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D047169:Cyclotides / Q000737:chemistry; D018076:DNA, Complementary / Q000737:chemistry* / Q000378:metabolism; D019143:Evolution, Molecular; D017343:Genes, Plant; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D005810:Multigene Family; D010455:Peptides / Q000737:chemistry; D011487:Protein Conformation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D011522:Protons; D012313:RNA / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D032413:Viola
D047169:Cyclotides; D018076:DNA, Complementary; D010455:Peptides; D011522:Protons; D012313:RNA