PDBsum entry 3siq

Ligase

PDB id: 3siq

Contents

Protein chains

103 a.a.

95 a.a.

97 a.a.

95 a.a.

Metals

_ZN ×6

Waters ×4

PDB id:

3siq

Name:

Ligase

Title:

Crystal structure of autoinhibited diap1-bir1 domain

Structure:

Apoptosis 1 inhibitor. Chain: a, b, c, d, e, f. Fragment: bir1 domain (unp residies 1-136). Synonym: e3 ubiquitin-protein ligase th, inhibitor of apoptosis 1, diap1, protein thread. Engineered: yes. Mutation: yes

Source:

Drosophila melanogaster. Fruit fly. Organism_taxid: 7227. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.40Å R-factor: 0.150 R-free: 0.217

Authors:

X.Li,J.Wang,Y.Shi

Key ref:

X.Li et al. (2011). Structural mechanisms of DIAP1 auto-inhibition and DIAP1-mediated inhibition of drICE. Nat Commun, 2, 408. PubMed id: 21811237 DOI: 10.1038/ncomms1418

Date:

20-Jun-11 Release date: 10-Aug-11

Protein chain

Q24306  (DIAP1_DROME) -  Death-associated inhibitor of apoptosis 1 from Drosophila melanogaster

Seq: 438 a.a.

Struc: 103 a.a.*

Protein chain

Q24306  (DIAP1_DROME) -  Death-associated inhibitor of apoptosis 1 from Drosophila melanogaster

Seq: 438 a.a.

Struc: 95 a.a.*

Protein chains

Q24306  (DIAP1_DROME) -  Death-associated inhibitor of apoptosis 1 from Drosophila melanogaster

Seq: 438 a.a.

Struc: 97 a.a.*

Protein chain

Q24306  (DIAP1_DROME) -  Death-associated inhibitor of apoptosis 1 from Drosophila melanogaster

Seq: 438 a.a.

Struc: 95 a.a.*

* PDB and UniProt seqs differ at 27 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains A, B, C, D, E, F: 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: 10.1038/ncomms1418

Nat Commun 2:408 (2011)

PubMed id: 21811237

Structural mechanisms of DIAP1 auto-inhibition and DIAP1-mediated inhibition of drICE.

X.Li, J.Wang, Y.Shi.

ABSTRACT

The Drosophila inhibitor of apoptosis protein DIAP1 exists in an auto-inhibited conformation, unable to suppress the effector caspase drICE. Auto-inhibition is disabled by caspase-mediated cleavage of DIAP1 after Asp20. The cleaved DIAP1 binds to mature drICE, inhibits its protease activity, and, presumably, also targets drICE for ubiquitylation. DIAP1-mediated suppression of drICE is effectively antagonized by the pro-apoptotic proteins Reaper, Hid, and Grim (RHG). Despite rigorous effort, the molecular mechanisms behind these observations are enigmatic. Here we report a 2.4 Å crystal structure of uncleaved DIAP1-BIR1, which reveals how the amino-terminal sequences recognize a conserved surface groove in BIR1 to achieve auto-inhibition, and a 3.5 Å crystal structure of active drICE bound to cleaved DIAP1-BIR1, which provides a structural explanation to DIAP1-mediated inhibition of drICE. These structures and associated biochemical analyses, together with published reports, define the molecular determinants that govern the interplay among DIAP1, drICE and the RHG proteins.