PDBsum entry 1jd5

Hydrolase/peptide

PDB id: 1jd5

Contents

Protein chain

105 a.a. *

Ligands

ALA-ILE-ALA-TYR-PHE-ILE-PRO-ASP

Metals

_ZN

* Residue conservation analysis

PDB id:

1jd5

Name:

Hydrolase/peptide

Title:

Crystal structure of diap1-bir2/grim

Structure:

Apoptosis 1 inhibitor. Chain: a. Synonym: diap1. Engineered: yes. Cell death protein grim. Chain: b. Engineered: yes

Source:

Drosophila melanogaster. Fruit fly. Organism_taxid: 7227. Gene: diap1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Other_details: this peptide was chemically synthesized. The sequence is naturally found in drosophila melanogaster (fruit fly).

Biol. unit:

Tetramer (from PQS)

Resolution:

1.90Å R-factor: 0.202 R-free: 0.243

Authors:

J.W.Wu,A.E.Cocina,J.Chai,B.A.Hay,Y.Shi

Key ref:

J.W.Wu et al. (2001). Structural analysis of a functional DIAP1 fragment bound to grim and hid peptides. Mol Cell, 8, 95. PubMed id: 11511363 DOI: 10.1016/S1097-2765(01)00282-9

Date:

12-Jun-01 Release date: 05-Dec-01

Protein chain

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

Seq: 438 a.a.

Struc: 105 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: 10.1016/S1097-2765(01)00282-9

Mol Cell 8:95 (2001)

PubMed id: 11511363

Structural analysis of a functional DIAP1 fragment bound to grim and hid peptides.

J.W.Wu, A.E.Cocina, J.Chai, B.A.Hay, Y.Shi.

ABSTRACT

The inhibitor of apoptosis protein DIAP1 suppresses apoptosis in Drosophila, with the second BIR domain (BIR2) playing an important role. Three proteins, Hid, Grim, and Reaper, promote apoptosis, in part by binding to DIAP1 through their conserved N-terminal sequences. The crystal structures of DIAP1-BIR2 by itself and in complex with the N-terminal peptides from Hid and Grim reveal that these peptides bind a surface groove on DIAP1, with the first four amino acids mimicking the binding of the Smac tetrapeptide to XIAP. The next 3 residues also contribute to binding through hydrophobic interactions. Interestingly, peptide binding induces the formation of an additional alpha helix in DIAP1. Our study reveals the structural conservation and diversity necessary for the binding of IAPs by the Drosophila Hid/Grim/Reaper and the mammalian Smac proteins.

Selected figure(s)

Figure 1.
Figure 1. Overall Structure of the DIAP1-BIR2 Domain by Itself (A) and in Complex with the Grim (B) or Hid (C) PeptideThe DIAP1-BIR2 domain is shown in cyan and the bound Grim and Hid peptides are highlighted in orange and pink, respectively. The zinc atom in the BIR domain is colored red, while its coordinating residues are shown in yellow. Some of the secondary structural elements are labeled. In (D), the structures of DIAP1-BIR2 by itself and in complex with the Hid/Grim peptides are superimposed with that of XIAP-BIR3 in complex with the Smac tetrapeptide (Protein Data Bank code 1G73). The DIAP1-BIR2 and XIAP-BIR3 are shown in cyan and purple, respectively. The bound Grim and Hid peptides are highlighted in orange and pink, respectively, while the Smac tetrapeptide is represented in green. Helix α6, highlighted in red, is only present in the peptide-bound BIR2

Figure 4.
Figure 4. Specific Recognition of DIAP1-BIR2 by the Hid and Grim Peptides(A) Stereo view of the interface between DIAP1-BIR2, colored cyan, and the bound Grim peptide, in orange. The important residues in DIAP1 are highlighted in yellow. Hydrogen bonds are represented by red dashed lines. The same DIAP1-BIR2 orientation is maintained for (C).(B) Close up view of the hydrophobic interface between DIAP1-BIR2 and the Grim peptide. The coloring scheme is the same as in (A).(C) Stereo view of the interface between DIAP1-BIR2 and the bound Hid peptide, shown in pink

The above figures are reprinted by permission from Cell Press: Mol Cell (2001, 8, 95-0) copyright 2001.

Figures were selected by an automated process.