PDBsum entry 2of5

Apoptosis

PDB id: 2of5

Contents

Protein chains

(+ 1 more) 91 a.a. *

100 a.a. *

Waters ×21

* Residue conservation analysis

PDB id:

2of5

Name:

Apoptosis

Title:

Oligomeric death domain complex

Structure:

Death domain-containing protein cradd. Chain: a, b, c, d, e, f, g. Synonym: caspase and rip adapter with death domain, rip-associated protein with a death domain. Engineered: yes. Leucine-rich repeat and death domain-containing protein. Chain: h, i, j, k, l. Synonym: p53-induced protein with a death domain. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: cradd, raidd. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Gene: lrdd, pidd.

Resolution:

3.20Å R-factor: 0.236 R-free: 0.275

Authors:

H.H.Park,E.Logette,S.Raunser,S.Cuenin,T.Walz,J.Tschopp,H.Wu

Key ref:

H.H.Park et al. (2007). Death domain assembly mechanism revealed by crystal structure of the oligomeric PIDDosome core complex. Cell, 128, 533-546. PubMed id: 17289572 DOI: 10.1016/j.cell.2007.01.019

Date:

02-Jan-07 Release date: 17-Apr-07

Protein chains

P78560  (CRADD_HUMAN) -  Death domain-containing protein CRADD from Homo sapiens

Seq: 199 a.a.

Struc: 91 a.a.

Protein chains

Q9HB75  (PIDD1_HUMAN) -  p53-induced death domain-containing protein 1 from Homo sapiens

Seq: 910 a.a.

Struc: 100 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class 1: Chains A, B, C, D, E, F, G: E.C.?
• Enzyme class 2: Chains H, I, J, K, L: E.C.3.4.21.- - ?????

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

DOI no: 10.1016/j.cell.2007.01.019

Cell 128:533-546 (2007)

PubMed id: 17289572

Death domain assembly mechanism revealed by crystal structure of the oligomeric PIDDosome core complex.

H.H.Park, E.Logette, S.Raunser, S.Cuenin, T.Walz, J.Tschopp, H.Wu.

ABSTRACT

Proteins of the death domain (DD) superfamily mediate assembly of oligomeric signaling complexes for the activation of caspases and kinases via unknown mechanisms. Here we report the crystal structure of the PIDD DD and RAIDD DD complex, which forms the core of the caspase-2-activating complex PIDDosome. Although RAIDD DD and PIDD DD are monomers, they assemble into a complex that comprises seven RAIDD DDs and five PIDD DDs. Despite the use of an asymmetric assembly mechanism, all DDs in the complex are in quasi-equivalent environments. The structure provided eight unique asymmetric interfaces, which can be classified into three types. These three types of interactions together cover a majority of the DD surface. Mutagenesis on almost all interfaces leads to disruption of the assembly, resulting in defective caspase-2 activation. The three types of interactions may represent most, if not all, modes of interactions in the DD superfamily for assembling complexes of different stoichiometry.

Selected figure(s)

Figure 4.
Figure 4. The Three Types of Interactions and Their Subtypes, a Total of Eight Interactions
(A) A schematic diagram for the locations of the three types of contacts in the PIDD DD:RAIDD DD complex.
(B) The three different subtypes of the type I interaction.
(C) The two different subtypes of the type II interaction.
(D) The three different subtypes of the type III interaction. Important residues and hydrogen bonding interactions are labeled.
(E) A hypothetical Fas DD:FADD DD complex constructed from the same three types of interactions. The same view is used as in (A), and the Fas DD:FADD DD complex may be considered as a portion of the PIDD DD:RAIDD DD complex composed of R7, R2, P2, R3, P3, and R4.

Figure 5.
Figure 5. Conservation, Plasticity, and Coverage of the Type I, II, and III Interactions
(A) Comparison of the R:P (red), R:R (blue), and P:P (green) subtypes of the type I interaction. One molecule in each subtype is superimposed.
(B) Comparison of the R:P (red) and R:R (blue) subtypes in the type II interaction. One molecule in each subtype is superimposed.
(C) Comparison of the R:P (red), R:R (blue), and P:P (green) subtypes in the type III interaction. One molecule in each subtype is superimposed.
(D) Comparison of the type I interaction (R2:P1) with the procaspase-9 CARD:Apaf-1 CARD interaction. R2 is superimposed with procaspase-9 CARD.
(E) Comparison of the type II interaction (R1:P1) with the Pelle DD:Tube DD interaction. R1 is superimposed with Pelle DD.
(F) The six types of regions of R5 in its interaction with neighboring DDs in the complex. Two views of R5 are shown. Green and red: type Ia and Ib regions. Magenta and blue: type IIa and IIb regions. Yellow and cyan: type IIIa and IIIb regions.
(G) Surface representation of R5, showing the same six surfaces of contacts. Same color coding is used as in (F). The small gray area of surface at the 180° rotated view of R5 that does not contact any of the six immediate neighboring molecules interacts with R2 and P3 in the three-dimensional assembly.

The above figures are reprinted by permission from Cell Press: Cell (2007, 128, 533-546) copyright 2007.

Figures were selected by an automated process.