Structures, Domains and Functions in Cell Death (DD, DED, CARD, PYD)

Abstract

The death domain (DD), death effector domain (DED), caspase‐recruitment domain (CARD) and pyrin domain (PYD) are subfamilies of the DD superfamily. By mediating homotypic interactions, these proteins play important roles in the assembly and activation of apoptotic signalling complexes. They are responsible for caspase recruitment and for formation of oligomeric platforms for signalling. DD superfamily proteins have a common six‐helical bundle fold and show different surface features for each of the subfamilies. Most interestingly, the homotypic interactions within each subfamily are mostly mediated by asymmetric contacts, in which different surfaces of the interaction partners are adjacent to each other. The DD superfamily proteins appear to use three common types of asymmetric interactions to assemble into large oligomeric complexes.

Key concepts

  • Death domains (DDs), death effector domains (DEDs), caspase‐recruitment domains (CARDs) and pyrin domains (PYDs) are protein:protein interaction modules for formation of caspase‐activating complexes.

  • DDs, DEDs, CARDs and PYDs share a common six‐helical bundle fold.

  • Interactions within these domains are mostly asymmetric and conserved.

Keywords: death domain (DD); death effector domain (DED); tandem DED; caspase recruitment domain (CARD); pyrin domain (PYD); structure

Figure 1.

Domain organizations of selective proteins containing the DD superfamily domains. Abbreviations: CARD, caspase recruitment domain; CRD, cysteine‐rich domain; DD, death domain; DED, death effector domain; GUK, guanylate kinase‐like; LRR, leucine‐rich repeat; NOD, nucleotide‐binding oligomerization domain; PYD, pyrin domain; TIR, toll/interleukin 1 receptor and TM, transmembrane domain.

Figure 2.

Ribbon diagrams for each subfamily of the DD superfamily: (a) Fas DD, (b) FADDDED, (c) Apaf‐1CARD and (d) NLRP1 PYD. (e) Electrostatic surface representation of Apaf‐1CARD. (f) Stick model for the hydrogen‐bonding interactions in the charge triad of MC159 DED1. (g) Electrostatic surface representation of MC159 DED1 and DED2, showing the dumbbell‐shaped structure, the rich charges on one face and the location of the hydrophobic patch. Panels (f) and (g) are taken from Yang et al..

Figure 3.

Structural features of interactions in the DD superfamily. (a) Pelle DD:Tube DD complex, as a type II interaction. (b) Apaf‐1 CARD:procaspase‐9 CARD complex, as a type I interaction. (c) MC159 DED1:DED2 interaction, as a type I interaction. (d) Overview of the PIDD DD:RAIDD DD complex in two orthogonal orientations. (e) Superposition of the eight unique interactions in the PIDD DD:RAIDD DD complex. R:RAIDD DD; P:PIDDDD. There are three type I interactions, two type II interactions and three type III interactions. (f) Tetrameric Fas DD:FADDDD complex. Panels (d) and (e) are taken from Park et al..

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Wu, Hao, and Lo, Yu‐Chih(Dec 2009) Structures, Domains and Functions in Cell Death (DD, DED, CARD, PYD). In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0021579]