J Biol Chem. 2011 Oct 14;286(41):35874-82. doi: 10.1074/jbc.M111.242321. Epub 2011 Aug 23.

Interaction patches of procaspase-1 caspase recruitment domains (CARDs) are differently involved in procaspase-1 activation and receptor-interacting protein 2 (RIP2)-dependent nuclear factor kappaB signaling.External

Kersse, K., Lamkanfi, M., Bertrand, M. J., Vanden Berghe, T., Vandenabeele, P.,
--- - Department for Molecular Biomedical Research, Flanders Institute for Biotechnology (VIB), B-9052 Ghent (Zwijnaarde), Belgium.
Protein interaction domains belonging to the death domain-fold superfamily are six-helix bundles that mediate the assembly of large protein complexes involved in apoptotic and inflammatory signaling. Typically, death domains (DDs), a subfamily of the death domain-fold superfamily, harbor six delineated interaction patches on their surfaces that mediate three distinct and conserved types of interaction designated as types I, II, and III. Here, we show that caspase recruitment domains (CARDs), another subfamily of the death domain-fold superfamily, multimerize by employing at least two of the three reported interaction types that were identified in DDs. On the one hand, the CARD of procaspase-1 binds the apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) through a type I interaction that involves a patch surrounding residue Asp-27. On the other hand, the CARD of procaspase-1 auto-oligomerizes through a type III interaction involving a patch surrounding residue Arg-45. This oligomerization allows binding of receptor-interacting protein 2 (RIP2). In addition, we show that a 1:1 interaction between ASC and procaspase-1 is sufficient for procaspase-1 to gain proteolytic activity, whereas the formation of a higher order CARD complex involving ASC, procaspase-1, and RIP2 is required for effective procaspase-1-mediated NF-kappaB activation. These findings indicate that the CARD of procaspase-1 is differently involved in the formation of procaspase-1 activating platforms and procaspase-1-mediated, RIP2-dependent NF-kappaB activation.
PMID: 21862576External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vivo interaction
  Endogenous
expression
Overexpression DD1 DD2 Reference
Family DD1 DD2 Method Species Region Species Region
CARD ASC Link Caspase1 Co-immunoprecipitation HEK239 Human Not specified Human Not specified 21862576
CARD Caspase1 Link Caspase1 Co-immunoprecipitation HEK239 Human Not specified Human Not specified 21862576
CARD Caspase1 Link RIPK2 Co-immunoprecipitation HEK239 Human Not specified Not specified Not specified 21862576
(Link: click this icon to show interactions only between the two corresponding DDs)
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
Characterization
  Stoichiometry Affinity Protein-Protein interface Reference
Family DD1 DD2 Method Mutation Complex structure
CARD ASC Link Caspase1 Co-immunoprecipitation D27G, R45D (Caspase1) 21862576
CARD Caspase1 Link Caspase1 Co-immunoprecipitation D27G, R45D (Caspase1) 21862576
CARD Caspase1 Link RIPK2 Co-immunoprecipitation D27G, R45D (Caspase1) 21862576
(Link: click this icon to show interactions only between the two corresponding DDs)
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
Functional Role
Family DD1 DD2 Method Death-related Death-unrelated Reference
CARD ASC Link Caspase1 Luciferase assay NF-kB activation 21862576
(Link: click this icon to show interactions only between the two corresponding DDs)