Caspase

Caspase (CASP) are cysteine-aspartic proteases (see Protease) which function in apoptosis, necrosis and inflammation. Twelve CASP have been identified in human. CASP is synthesized as an inactive pro-CASP with a prodomain which is being cleaved off to render them active. The X-linked inhibitor of apoptosis protein (XIAP) with its baculoviral IAP repeat (BIR) domain is an inhibitor of CASP. The CASP recruitment domain (CARD) mediates signaling events that are associated with various human diseases including cancer, neuro-degenerative diseases and immune disorders^[1].

CASP-1 (or Interleukin-1 beta converting enzyme, ICE) cleaves precursor cytokine interleukin 1-β and interleukin 18 into mature protein. See:

Human Caspase-1

CASP-3 or (Apopain; Cysteine protease CPP32) interacts with CASP-8 and CASP-9 during cell apoptosis. See:

Sandox Bay Serrano

Student Projects for UMass Chemistry 423 Spring 2012-5
Caspase-3 Regulatory Mechanisms

CASP-4 binds the lipid moiety of lipopolysaccharide to induce the activation of non-canonical inflammasome^[2].
CASP-6 is involved in the activation of cascade of caspases during apoptosis. See:

Molecular Playground/Caspase-6 (new)

Caspase-6 and neurodegeneration

CASP-7 is a heterodimer consisting of P20 (human residues 1-198) and P11 (human residues 199-303) subunits. CASP-7 catalytic domain consists of residues 57-303. is an important initiator CASP and drICE is an effector of apoptosis CASP in Drosophila melanogaster. See:

Molecular Playground/Caspase-7 Dynamics

Molecular Playground/Executioner Caspase-7

CASP-9 is an aspartic protease linked to mitochondrial death pathway. See:

Molecular Playground/Caspase-9 Regulation.

Metacaspase (MCASP) are arginine/lysine specific CASP. MCASP are found in plants and fungi.

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3D structures of caspase

Caspase 3D structures

CASP-2 subunit P18 (purple, yellow) and subunit P12 (green, cyan) complex with polypeptide inhibitor (salmon, blue), aspartic aldehyde and acetyl group, 1pyo

Drag the structure with the mouse to rotate

ReferencesReferences

↑ Park HH. Caspase recruitment domains for protein interactions in cellular signaling (Review). Int J Mol Med. 2019 Mar;43(3):1119-1127. doi: 10.3892/ijmm.2019.4060. Epub 2019, Jan 11. PMID:30664151 doi:http://dx.doi.org/10.3892/ijmm.2019.4060
↑ Lagrange B, Benaoudia S, Wallet P, Magnotti F, Provost A, Michal F, Martin A, Di Lorenzo F, Py BF, Molinaro A, Henry T. Human caspase-4 detects tetra-acylated LPS and cytosolic Francisella and functions differently from murine caspase-11. Nat Commun. 2018 Jan 16;9(1):242. doi: 10.1038/s41467-017-02682-y. PMID:29339744 doi:http://dx.doi.org/10.1038/s41467-017-02682-y
↑ Schweizer A, Briand C, Grutter MG. Crystal structure of caspase-2, apical initiator of the intrinsic apoptotic pathway. J Biol Chem. 2003 Oct 24;278(43):42441-7. Epub 2003 Aug 14. PMID:12920126 doi:http://dx.doi.org/10.1074/jbc.M304895200
↑ Wilson KP, Black JA, Thomson JA, Kim EE, Griffith JP, Navia MA, Murcko MA, Chambers SP, Aldape RA, Raybuck SA, et al.. Structure and mechanism of interleukin-1 beta converting enzyme. Nature. 1994 Jul 28;370(6487):270-5. PMID:8035875 doi:http://dx.doi.org/10.1038/370270a0

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Michal Harel, Alexander Berchansky

[1] Park HH. Caspase recruitment domains for protein interactions in cellular signaling (Review). Int J Mol Med. 2019 Mar;43(3):1119-1127. doi: 10.3892/ijmm.2019.4060. Epub 2019, Jan 11. PMID:30664151 doi:http://dx.doi.org/10.3892/ijmm.2019.4060

[2] Lagrange B, Benaoudia S, Wallet P, Magnotti F, Provost A, Michal F, Martin A, Di Lorenzo F, Py BF, Molinaro A, Henry T. Human caspase-4 detects tetra-acylated LPS and cytosolic Francisella and functions differently from murine caspase-11. Nat Commun. 2018 Jan 16;9(1):242. doi: 10.1038/s41467-017-02682-y. PMID:29339744 doi:http://dx.doi.org/10.1038/s41467-017-02682-y

[3] Schweizer A, Briand C, Grutter MG. Crystal structure of caspase-2, apical initiator of the intrinsic apoptotic pathway. J Biol Chem. 2003 Oct 24;278(43):42441-7. Epub 2003 Aug 14. PMID:12920126 doi:http://dx.doi.org/10.1074/jbc.M304895200

[4] Wilson KP, Black JA, Thomson JA, Kim EE, Griffith JP, Navia MA, Murcko MA, Chambers SP, Aldape RA, Raybuck SA, et al.. Structure and mechanism of interleukin-1 beta converting enzyme. Nature. 1994 Jul 28;370(6487):270-5. PMID:8035875 doi:http://dx.doi.org/10.1038/370270a0

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