1DF0

Crystal structure of M-Calpain

Summary for 1DF0

• Entry DOI: 10.2210/pdb1df0/pdb
• Related: 1AJ5 1ALV 1ALW 1DVI
• Descriptor: M-CALPAIN, CALPAIN (3 entities in total)
• Functional Keywords: cysteine protease, calmodulin, papain, catalytic triad, zymogen activation, c2 domain, protease, zymogen, calpain, hydrolase
• Biological source: Rattus norvegicus (Norway rat); More
• Cellular location: Cytoplasm : Q07009 Q64537
• Total number of polymer chains: 2
• Total formula weight: 101299.02

Authors

Hosfield, C.M.,Elce, J.S.,Davies, P.L.,Jia, Z. (deposition date: 1999-11-16, release date: 2000-06-21, Last modification date: 2024-02-07)

Primary citation

Hosfield, C.M.,Elce, J.S.,Davies, P.L.,Jia, Z.
Crystal structure of calpain reveals the structural basis for Ca(2+)-dependent protease activity and a novel mode of enzyme activation.
EMBO J., 18:6880-6889, 1999

PubMed Abstract: The combination of thiol protease activity and calmodulin-like EF-hands is a feature unique to the calpains. The regulatory mechanisms governing calpain activity are complex, and the nature of the Ca(2+)-induced switch between inactive and active forms has remained elusive in the absence of structural information. We describe here the 2.6 A crystal structure of m-calpain in the Ca(2+)-free form, which illustrates the structural basis for the inactivity of calpain in the absence of Ca(2+). It also reveals an unusual thiol protease fold, which is associated with Ca(2+)-binding domains through heterodimerization and a C(2)-like beta-sandwich domain. Strikingly, the structure shows that the catalytic triad is not assembled, indicating that Ca(2+)-binding must induce conformational changes that re-orient the protease domains to form a functional active site. The alpha-helical N-terminal anchor of the catalytic subunit does not occupy the active site but inhibits its assembly and regulates Ca(2+)-sensitivity through association with the regulatory subunit. This Ca(2+)-dependent activation mechanism is clearly distinct from those of classical proteases.

PubMed: 10601010
DOI: 10.1093/emboj/18.24.6880

Experimental method

X-RAY DIFFRACTION (2.6 Å)