Calpain

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.
CAP2 limits the extent of neuronal plasticity and learning^[2].
CAP3 is expressed in skeletal muscles and regulates sarcomere remodelling^[3].
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. ^[4]

. Water molecules are shown as red spheres.
.
.
.^[5]

3D structures of calpain

Calpain 3D structures

Human calpain1 large subunit complex with inhibitor and Ca+2 ions (green) (PDB entry 1zcm)

Drag the structure with the mouse to rotate

ReferencesReferences

↑ Goll DE, Thompson VF, Li H, Wei W, Cong J. The calpain system. Physiol Rev. 2003 Jul;83(3):731-801. PMID:12843408 doi:http://dx.doi.org/10.1152/physrev.00029.2002
↑ Wang Y, Liu Y, Bi X, Baudry M. Calpain-1 and Calpain-2 in the Brain: New Evidence for a Critical Role of Calpain-2 in Neuronal Death. Cells. 2020 Dec 16;9(12):2698. PMID:33339205 doi:10.3390/cells9122698
↑ Duguez S, Bartoli M, Richard I. Calpain 3: a key regulator of the sarcomere? FEBS J. 2006 Aug;273(15):3427-36. PMID:16884488 doi:10.1111/j.1742-4658.2006.05351.x
↑ 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:http://dx.doi.org/10.1021/bi052077b

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky

[1] Goll DE, Thompson VF, Li H, Wei W, Cong J. The calpain system. Physiol Rev. 2003 Jul;83(3):731-801. PMID:12843408 doi:http://dx.doi.org/10.1152/physrev.00029.2002

[2] Wang Y, Liu Y, Bi X, Baudry M. Calpain-1 and Calpain-2 in the Brain: New Evidence for a Critical Role of Calpain-2 in Neuronal Death. Cells. 2020 Dec 16;9(12):2698. PMID:33339205 doi:10.3390/cells9122698

[3] Duguez S, Bartoli M, Richard I. Calpain 3: a key regulator of the sarcomere? FEBS J. 2006 Aug;273(15):3427-36. PMID:16884488 doi:10.1111/j.1742-4658.2006.05351.x

[4] 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

[5] 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:http://dx.doi.org/10.1021/bi052077b

[1]

[2]

[3]

[4]

[5]