Function
Calpains (CAP) are calcium-dependent cysteine proteases. CAPs are regulated by Ca+2 concentration, phosphorylation and calpastatin.[1] The CAP family contains 14 members.
- CAP1 (or mu-CAP) and CAP2 (or M-CAP) T are the best characterized CAPs.
- CAP7 is atypical CAP that lacks a penta-EF-hand domain.
- CAP8 and CAP9 are involved in the mucosal defense against stress-induced gastropathies.
- CAP9 has been identified as the tumor suppressor for gastric cancer.
- CAP13 is expressed in testis and lungs.
Disease
CAP3 defects lead to a certain muscular dystrophy. Defective CAPs have a role in neurodegeneration.
Structural highlights
CAP is a heterodimer containing a small 28kDa regulatory subunit which is identical for all CAPs and a large 80kDa catalytic subunit. CAP undergoes conformational change upon binding of Ca+2 ions resulting in closing of its active site cleft and activation as a cysteine protease. [2]
3D structures of calpain
Calpain 3D structures
- ↑ Goll DE, Thompson VF, Li H, Wei W, Cong J. The calpain system. Physiol Rev. 2003 Jul;83(3):731-801. PMID:12843408 doi:https://dx.doi.org/10.1152/physrev.00029.2002
- ↑ Moldoveanu T, Hosfield CM, Lim D, Elce JS, Jia Z, Davies PL. A Ca(2+) switch aligns the active site of calpain. Cell. 2002 Mar 8;108(5):649-60. PMID:11893336
- ↑ Li Q, Hanzlik RP, Weaver RF, Schonbrunn E. Molecular mode of action of a covalently inhibiting peptidomimetic on the human calpain protease core. Biochemistry. 2006 Jan 24;45(3):701-8. PMID:16411745 doi:https://dx.doi.org/10.1021/bi052077b
