PDBsum entry 2way

Hydrolase

PDB id: 2way

Contents

Protein chains

153 a.a. *

26 a.a. *

30 a.a. *

Ligands

GOL ×4

Waters ×111

* Residue conservation analysis

PDB id:

2way

Name:

Hydrolase

Title:

Structure of the human ddx6 c-terminal domain in complex with an edc3- fdf peptide

Structure:

Atp-dependent RNA helicase ddx6. Chain: a, c. Fragment: c-terminal domain, residues 296-483. Synonym: human ddx6, dead box protein 6, atp-dependent RNA helicase p54, oncogene rck. Engineered: yes. Enhancer of mRNA-decapping protein 3. Chain: b, d. Fragment: fdf peptide, residues 192-228.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.30Å R-factor: 0.214 R-free: 0.275

Authors:

F.Tritschler,O.Weichenrieder

Key ref:

F.Tritschler et al. (2009). Structural basis for the mutually exclusive anchoring of P body components EDC3 and Tral to the DEAD box protein DDX6/Me31B. Mol Cell, 33, 661-668. PubMed id: 19285948 DOI: 10.1016/j.molcel.2009.02.014

Date:

18-Feb-09 Release date: 24-Mar-09

Protein chains

P26196  (DDX6_HUMAN) -  Probable ATP-dependent RNA helicase DDX6 from Homo sapiens

Seq: 483 a.a.

Struc: 153 a.a.

Protein chain

Q96F86  (EDC3_HUMAN) -  Enhancer of mRNA-decapping protein 3 from Homo sapiens

Seq: 508 a.a.

Struc: 26 a.a.

Protein chain

Q96F86  (EDC3_HUMAN) -  Enhancer of mRNA-decapping protein 3 from Homo sapiens

Seq: 508 a.a.

Struc: 30 a.a.

Enzyme reactions

• Enzyme class: Chains A, C: E.C.3.6.4.13 - Rna helicase.
• Reaction: ATP + H2O = ADP + phosphate + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/j.molcel.2009.02.014

Mol Cell 33:661-668 (2009)

PubMed id: 19285948

Structural basis for the mutually exclusive anchoring of P body components EDC3 and Tral to the DEAD box protein DDX6/Me31B.

F.Tritschler, J.E.Braun, A.Eulalio, V.Truffault, E.Izaurralde, O.Weichenrieder.

ABSTRACT

The DEAD box helicase DDX6/Me31B functions in translational repression and mRNA decapping. How particular RNA helicases are recruited specifically to distinct functional complexes is poorly understood. We present the crystal structure of the DDX6 C-terminal RecA-like domain bound to a highly conserved FDF sequence motif in the decapping activator EDC3. The FDF peptide adopts an alpha-helical conformation upon binding to DDX6, occupying a shallow groove opposite to the DDX6 surface involved in RNA binding and ATP hydrolysis. Mutagenesis of Me31B shows the relevance of the FDF interaction surface both for Me31B's accumulation in P bodies and for its ability to repress the expression of bound mRNAs. The translational repressor Tral contains a similar FDF motif. Together with mutational and competition studies, the structure reveals why the interactions of Me31B with EDC3 and Tral are mutually exclusive and how the respective decapping and translational repressor complexes might hook onto an mRNA substrate.

Selected figure(s)

Figure 1.
Figure 1. Structure of the DDX6-C/EDC3-FDF Heterodimer
(A) Domain organization of DDX6 and EDC3. The structured part of the DDX6 C-terminal domain is shown in gray, with the conserved helicase motifs in purple. The EDC3-FDF peptide is highlighted in salmon. Numbers correspond to the human proteins.
(B) Ribbon diagrams of the complex colored as in (A). Side chains for the EDC3-FDF and EDC3-FDK motifs and for DDX6-His312 are shown as sticks.
(C and D) Electrostatic potentials were mapped onto the respective molecular surface and contoured from −5 kT/e (red) to +5 kT/e (blue). In (C), EDC3-FDF is represented as sticks (carbons in yellow, oxygens in red, nitrogens in blue) on the molecular surface of DDX6-C. (D) shows the molecular surface of the complex and changes in charge distribution.

Figure 3.
Figure 3. Molecular Interface between DDX6-C and EDC3-FDF
DDX6-C (gray) and EDC3-FDF (salmon) are shown as ribbons with selected side-chain and main-chain atoms as sticks (oxygens in red, nitrogens in blue, sulfurs in yellow). Fixed water molecules are shown as red spheres and hydrogen bonds and salt bridges as dotted lines.
(A) Interactions of the N-terminal loop, the FDF motif, and α helix H1. The four residues mutated in DDX6-C^Mut-1 have boxed labels.
(B) Interactions of the N-terminal loop, the FDF motif, and α helix H1. β strand β8 is drawn as a loop for clarity.
(C) Interactions of the FDK motif and α helix H2. Equivalent residues mutated in Me31B^Mut-2 have boxed labels.

The above figures are reprinted by permission from Cell Press: Mol Cell (2009, 33, 661-668) copyright 2009.

Figures were selected by an automated process.