PDBsum entry 3eb5

Apoptosis

PDB id: 3eb5

Contents

Protein chain

65 a.a. *

Metals

_NA

_ZN ×2

Waters ×25

* Residue conservation analysis

PDB id:

3eb5

Name:

Apoptosis

Title:

Structure of the ciap2 ring domain

Structure:

Baculoviral iap repeat-containing protein 3. Chain: a. Fragment: ring domain (unp residues 536 to 604). Synonym: inhibitor of apoptosis protein 1, hiap-1, hiap1, c-iap2, tnfr2-traf-signaling complex protein 1, iap homolog c, apoptosis inhibitor 2, api2, ring finger protein 49. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: birc3, api2, iap1, mihc, rnf49. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.00Å R-factor: 0.219 R-free: 0.275

Authors:

P.D.Mace,K.Linke,C.A.Smith,C.L.Day

Key ref:

P.D.Mace et al. (2008). Structures of the cIAP2 RING Domain Reveal Conformational Changes Associated with Ubiquitin-conjugating Enzyme (E2) Recruitment. J Biol Chem, 283, 31633-31640. PubMed id: 18784070 DOI: 10.1074/jbc.M804753200

Date:

27-Aug-08 Release date: 09-Sep-08

Protein chain

Q13489  (BIRC3_HUMAN) -  Baculoviral IAP repeat-containing protein 3 from Homo sapiens

Seq: 604 a.a.

Struc: 65 a.a.

Enzyme reactions

• Enzyme class: E.C.2.3.2.27 - RING-type E3 ubiquitin transferase.
• Reaction: S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N₆- ubiquitinyl-[acceptor protein]-L-lysine

DOI no: 10.1074/jbc.M804753200

J Biol Chem 283:31633-31640 (2008)

PubMed id: 18784070

Structures of the cIAP2 RING Domain Reveal Conformational Changes Associated with Ubiquitin-conjugating Enzyme (E2) Recruitment.

P.D.Mace, K.Linke, R.Feltham, F.R.Schumacher, C.A.Smith, D.L.Vaux, J.Silke, C.L.Day.

ABSTRACT

Inhibitor of apoptosis (IAP) proteins are key negative regulators of cell death that are highly expressed in many cancers. Cell death caused by antagonists that bind to IAP proteins is associated with their ubiquitylation and degradation. The RING domain at the C terminus of IAP proteins is pivotal. Here we report the crystal structures of the cIAP2 RING domain homodimer alone, and bound to the ubiquitin-conjugating (E2) enzyme UbcH5b. These structures show that small changes in the RING domain accompany E2 binding. By mutating residues at the E2-binding surface, we show that autoubiquitylation is required for regulation of IAP abundance. Dimer formation is also critical, and mutation of a single C-terminal residue abrogated dimer formation and E3 ligase activity was diminished. We further demonstrate that disruption of E2 binding, or dimerization, stabilizes IAP proteins against IAP antagonists in vivo.

Selected figure(s)

Figure 3.
A symmetric complex is formed between cIAP2 RING dimers and UbcH5b. A, schematic representation of the crystal structure of cIAP2 RING domain (bright green) bound to UbcH5b (brown). The complex is symmetrical around the RING domain dimer interface, with one RING and one UbcH5b per asymmetric unit. B, comparison of the cIAP2 RING domain dimer (light green) with the cIAP2 RING-dimer from the complex structure (bright green). The RING domains were overlaid using secondary structure matching. C, close up view of the C terminus from free and E2-bound cIAP2 RING.

Figure 5.
Conserved features in RING domains mediate E2 recruitment. The surfaces of c-Cbl, cIAP2, and CHIP that interact with the E2 are colored according to electrostatic potential, and homologous regions are indicated in blue, yellow, and red. Residues that contribute to the additional interaction interfaces are highlighted in black.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2008, 283, 31633-31640) copyright 2008.

Figures were selected by an automated process.