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3D structure
Overview

The 3D structure of a portion of calpain (the PEF(L) domain of CAPNS1) was first solved in 1997 (Blanchard et al., 1997; Lin et al., 1997). In 1999 and 2000, whole 3D structures of the inactive forms (Ca2+-unbound) of rat and human m-calpain[CAPN2/S1], respectively, were determined (Hosfield et al., 1999; Strobl et al., 2000). Later, 3D structures of the protease (CysPc) domains of CAPN1, 2, and 9 in the presence of Ca2+ were elucidated, revealing one of the molecular mechanisms of calpain activation (Davis et al., 2007; Moldoveanu et al., 2002; Moldoveanu et al., 2003). Finally, the whole 3D structure of active rat CAPN2/S1[m-calpain] co-crystallized with calpastatin fragment was solved (Hanna et al., 2008; Moldoveanu et al., 2008).

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Fig. 9 Schematic of the 3D structure of inactive and active CAPN2/S1[m-calpain].

Schematic 3D ribbon structures superimposed on the surface-type structures of the inactive (Ca2+-free) and active (Ca2+- and calpastatin-bound) forms of human and rat CAPN2/S1[m-calpain], respectively, using the PDB data, 1KFX (Strobl et al., 2000) and 3DF0 (Moldoveanu et al., 2008). The active protease (CysPc) domain is formed by the fusion of the PC1 and PC2 core domains after the binding of a single Ca2+ by each of the Ca2+-binding site in both core domains (CBS-1 and -2). The active site is circled in black. Red balls represent Ca2+. Only a small part of the GR domain is visible because of its “soft” structure.

Abbreviations used for domain names:
CysPc: calpain-like cysteine protease sequence motif defined in the conserved domain database at the National Center for Biotechnology Information (cd00044), which is composed of two protease core domains 1 and 2 (PC1 and PC2).
PC1: protease core domain 1
PC2: protease core domain 2
CBS-1: Ca2+-binding site 1 in PC1 domain
CBS-2: Ca2+-binding site 2 in PC2 domain
CBSW: calpain-type beta-sandwich domain (formerly called "C2-domain-like (C2L)" domain)
PEF: penta-EF-hand domain

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