Crystal structure of a micro-like calpain reveals a partially activated conformation with low Ca2+ requirement.
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.
Pal
Gour P
GP
Department of Biochemistry, Queen's University, Kingston, Ontario K7L 3N6, Canada.
De Veyra
Teresa
T
Elce
John S
JS
Jia
Zongchao
Z
D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000737:chemistry*; D002154:Calpain / Q000737:chemistry*; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D051381:Rats
D002154:Calpain; C449002:mu-calpain; D002118:Calcium