Evolutionary relationships and protein domain architecture in an expanded calpain superfamily in kinetoplastid parasites

• Published in: Journal of molecular evolution Vol. 61; no. 6; pp. 742 - 757
• Main Authors: Ersfeld, Klaus, Barraclough, Helen, Gull, Keith
• Format: Journal Article
• Language: English
• Published: Germany Springer Nature B.V 01.12.2005
• Subjects: Acylation; Amino Acid Motifs; Amino Acid Sequence; Animals; Bacteria; Calcium-binding protein; Calmodulin; Calpain; Calpain - genetics; Catalytic activity; Conserved sequence; Databases, Protein; Domains; Eukaryotes; Evolution, Molecular; Fatty acids; Leishmania major; Leishmania major - genetics; Modular structures; Molecular Sequence Data; Parasites; Phylogeny; Protease; Protein Structure, Tertiary - genetics; Proteinase; Proteins; Sequence Alignment; Sequence Homology, Amino Acid; Trypanosoma brucei; Trypanosoma brucei brucei - genetics; Trypanosoma cruzi; Trypanosoma cruzi - genetics
• ISSN: 0022-2844; 1432-1432
• DOI: 10.1007/s00239-004-0272-8

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.