Evolutionary relationships and protein domain architecture in an expanded calpain superfamily in kinetoplastid parasites.
Employing whole-genome analysis we have characterized a large family of genes coding for calpain-related proteins in three kinetoplastid parasites. We have defined a total of 18 calpain-like sequences in Trypanosoma brucei, 27 in Leishmania major, and 24 in Trypanosoma cruzi. Sequence characterization revealed a well-conserved protease domain in most proteins, although residues critical for catalytic activity were frequently altered. Many of the proteins contain a novel N-terminal sequence motif unique to kinetoplastids. Furthermore, 24 of the sequences contain N-terminal fatty acid acylation motifs indicating association of these proteins with intracellular membranes. This extended family of proteins also includes a group of sequences that completely lack a protease domain but is specifically related to other kinetoplastid calpain-related proteins by a highly conserved N-terminal domain and by genomic organization. All sequences lack the C-terminal calmodulin-related calcium-binding domain typical of most mammalian calpains. Our analysis emphasizes the highly modular structure of calpains and calpain-like proteins, suggesting that they are involved in diverse cellular functions. The discovery of this surprisingly large family of calpain-like proteins in lower eukaryotes that combines novel and conserved sequence modules contributes to our understanding of the evolution of this abundant protein family.
Ersfeld
Klaus
K
Department of Biological Sciences, University of Hull, Hull, HU6 7RX, UK. k.ersfeld@hull.ac.uk
Barraclough
Helen
H
Gull
Keith
K
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002154:Calpain / Q000235:genetics*; D030562:Databases, Protein; D019143:Evolution, Molecular; D018320:Leishmania major / Q000235:genetics*; D008969:Molecular Sequence Data; D010802:Phylogeny; D017434:Protein Structure, Tertiary / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014346:Trypanosoma brucei brucei / Q000235:genetics*; D014349:Trypanosoma cruzi / Q000235:genetics*
D002154:Calpain