PDBsum entry 3dof

Signaling protein/hydrolase

PDB id: 3dof

Contents

Protein chains

189 a.a. *

120 a.a. *

Ligands

GTP

Metals

_MG

Waters ×15

* Residue conservation analysis

PDB id:

3dof

Name:

Signaling protein/hydrolase

Title:

Complex of arl2 and bart, crystal form 2

Structure:

Adp-ribosylation factor-like protein 2. Chain: a. Engineered: yes. Adp-ribosylation factor-like protein 2-binding protein. Chain: b. Synonym: arf-like 2-binding protein, binder of arf2 protein 1. Engineered: yes

Source:

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

Resolution:

3.30Å R-factor: 0.255 R-free: 0.294

Authors:

T.Zhang,S.Li,J.Ding

Key ref:

T.Zhang et al. (2009). Crystal structure of the ARL2-GTP-BART complex reveals a novel recognition and binding mode of small GTPase with effector. Structure, 17, 602-610. PubMed id: 19368893 DOI: 10.1016/j.str.2009.01.014

Date:

04-Jul-08 Release date: 03-Mar-09

Protein chain

P36404  (ARL2_HUMAN) -  ADP-ribosylation factor-like protein 2 from Homo sapiens

Seq: 184 a.a.

Struc: 189 a.a.

Protein chain

Q9Y2Y0  (AR2BP_HUMAN) -  ADP-ribosylation factor-like protein 2-binding protein from Homo sapiens

Seq: 163 a.a.

Struc: 120 a.a.

DOI no: 10.1016/j.str.2009.01.014

Structure 17:602-610 (2009)

PubMed id: 19368893

Crystal structure of the ARL2-GTP-BART complex reveals a novel recognition and binding mode of small GTPase with effector.

T.Zhang, S.Li, Y.Zhang, C.Zhong, Z.Lai, J.Ding.

ABSTRACT

ARL2 is a member of the ADP-ribosylation factor family but has unique biochemical features. BART is an effector of ARL2 that is essential for nuclear retention of STAT3 and may also be involved in mitochondria transport and apoptosis. Here we report the crystal structure and biochemical characterization of human ARL2-GTP-BART complex. ARL2-GTP assumes a typical small GTPase fold with a unique N-terminal alpha helix conformation. BART consists of a six alpha helix bundle. The interactions between ARL2 and BART involve two interfaces: a conserved N-terminal LLXIL motif of ARL2 is embedded in a hydrophobic cleft of BART and the switch regions of ARL2 interact with helix alpha3 of BART. Both interfaces are essential for the binding as verified by mutagenesis study. This novel recognition and binding mode is different from that of other small GTPase-effector interactions and provides molecular basis for the high specificity of ARL2 for BART.

Selected figure(s)

Figure 1.
Figure 1. Structure of the ARL2-GTP-BART Complex
(A) A stereo view of the ARL2-GTP-BART complex. ARL2 is colored in yellow with the N-terminal α helix in cyan and the switch I, switch II, and inter-switch regions in magenta, orange, and blue, respectively. The bound GTP is shown with a ball-and-stick model and the Mg^2+ ion in a green sphere. BART is colored in green with the secondary structures labeled.
(B) A stereo view of a representative difference Fourier Fo-Fc map (2σ contour level) in the interaction interface of the ARL2-BART complex in the region of helix α1 of ARL2 and helix α4 of BART.
(C) Superposition of ARL2-GTP in the ARL2-GTP-BART (red) and ARL2-GTP-PDEδ complexes (blue) and ARL3-GDP (yellow) showing the overall conformational differences.
(D) Superposition of the crystal structure of BART in the ARL2-GTP-BART complex (green) and the NMR solution structure of BART alone (yellow) showing the overall conformational differences.

Figure 2.
Figure 2. Interactions between ARL2-GTP and BART
(A) A stereo view showing the interactions between ARL2 and BART at interface I. Helix α1 of ARL2 (cyan) is embedded in a hydrophobic cleft formed by helices α3, α4, and α5 of BART (green).
(B) A stereo view showing the interactions between ARL2 and BART at interface II. The switch regions of ARL2 (switches I and II and the inter-switch region in magenta, orange, and blue, respectively) have both hydrophobic and hydrophilic interactions with the N terminus of helix α3 and the following loop of BART (green). The hydrogen-bonding interactions are indicated by dashed lines.
(C) A schematic diagram showing the hydrophobic contacts between ARL2 and BART.
(D) A schematic diagram showing the hydrogen-bonding interactions between ARL2 and BART.
(E) In vitro binding assay of the wild-type and mutant ARL2 with the GST-fused wild-type BART. GST cannot bind to ARL2 and thus was used as the negative control.
(F) In vitro binding assay of the wild-type ARL2 with the GST-fused wild-type and mutant BART.

The above figures are reprinted by permission from Cell Press: Structure (2009, 17, 602-610) copyright 2009.

Figures were selected by an automated process.