PDBsum entry: 1by1

Transport protein

PDB id: 1by1

Contents

Protein chain

209 a.a. *

* Residue conservation analysis

PDB id:

1by1

Name:

Transport protein

Title:

Dbl homology domain from beta-pix

Structure:

Protein (pix). Chain: a. Fragment: dbl homology domain. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

NMR struc:

20 models

Authors:

B.Aghazadeh,K.Zhu,T.J.Kubiseski,G.A.Liu,T.Pawson,Y.Zheng, M.K.Rosen

Key ref:

B.Aghazadeh et al. (1998). Structure and mutagenesis of the Dbl homology domain. Nat Struct Biol, 5, 1098-1107. PubMed id: 9846881 DOI: 10.1038/4209

Date:

22-Oct-98 Release date: 24-Oct-99

Protein chain

Q14155  (ARHG7_HUMAN) -  Rho guanine nucleotide exchange factor 7

Seq: 803 a.a.

Struc: 209 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 

• Cellular component: intracellular (1 term)
• Biological process: regulation of Rho protein signal transduction (1 term)
• Biochemical function: guanyl-nucleotide exchange factor activity (2 terms)

DOI no: 10.1038/4209

Nat Struct Biol 5:1098-1107 (1998)

PubMed id: 9846881

Structure and mutagenesis of the Dbl homology domain.

B.Aghazadeh, K.Zhu, T.J.Kubiseski, G.A.Liu, T.Pawson, Y.Zheng, M.K.Rosen.

ABSTRACT

Guanine nucleotide exchange factors in the Dbl family activate Rho GTPases by accelerating dissociation of bound GDP, promoting acquisition of the GTP-bound state. Dbl proteins possess a approximately 200 residue catalytic Dbl-homology (DH) domain, that is arranged in tandem with a C-terminal pleckstrin homology (PH) domain in nearly all cases. Here we report the solution structure of the DH domain of human PAK-interacting exchange protein (betaPIX). The domain is composed of 11 alpha-helices that form a flattened, elongated bundle. The structure explains a large body of mutagenesis data, which, along with sequence comparisons, identify the GTPase interaction site as a surface formed by three conserved helices near the center of one face of the domain. Proximity of the site to the DH C-terminus suggests a means by which PH-ligand interactions may be coupled to DH-GTPase interactions to regulate signaling through the Dbl proteins in vivo.

Selected figure(s)

Figure 4.
Figure 4. a, Ribbons^80 depiction of a representative conformer from the final ensemble of DH domain structures. Side chains of residues Thr 104 and Gln 271/Glu 272, whose mutation in UNC-73 and Dbl respectively, abrogates GEF activity are shown in red. Side chains of conserved residues in the putative GTPase interaction site that are discussed in the text are blue. Side chains of residues lining the depression between helices J and K are green. The N- and C-termini are labeled in blue. Orientation is the same as in Fig. 3. b, View of the DH domain down the long axis of the molecule, rotated 90° about a horizontal axis relative to (a).

Figure 6.
Figure 6. a, Molecular surface of the DH domain oriented as in Fig. 3. Residues are color coded according to sequence conservation among the proteins listed in Fig. 1. The color scale varies from white, representing conservation in three or less Dbl domains, to red, representing conservation in all nine domains. Helices are labeled in black, and the N- and C-termini are labeled in white b, View following rotation of the surface by 180° about a vertical axis. Figures were created using the program GRASP^81.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (1998, 5, 1098-1107) copyright 1998.

Figures were selected by an automated process.