1QXP

Crystal Structure of a mu-like calpain reveals a partially activated conformation with low Ca(2+) requirement

(2003) Structure 11: 1521-1526

• PubMed: 14656436 Search on PubMed
• DOI: https://doi.org/10.1016/j.str.2003.11.007
• Primary Citation of Related Structures:  
  1QXP


• PubMed Abstract: 
  

  The two Ca2+-dependent cysteine proteases, micro- and m-calpain, are involved in various Ca2+-linked signal pathways but differ markedly in their Ca2+ requirements for activation. We have determined the structure of a micro-like calpain, which has 85% micro-calpain sequence (the first 48 and the last 62 residues of the large subunit are those from m-calpain) and a low Ca2+ requirement. This construct was used because micro-calpain itself is too poorly expressed. The structure of micro-like calpain is very similar in overall fold to that of m-calpain as expected, but differs significantly in two aspects. In comparison with m-calpain, the catalytic triad residues in micro-like calpain, His and Cys, are much closer together in the absence of Ca2+, and significant portions of the Ca2+ binding EF-hand motifs are disordered and more flexible. These structural differences imply that Ca2+-free micro-calpain may represent a partially activated structure, requiring lower Ca2+ concentration to trigger its activation.

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Organizational Affiliation: 

Department of Biochemistry, Queen's University, Kingston, Ontario K7L 3N6, Canada.