PDBsum entry 1nf3

Signaling protein

PDB id: 1nf3

Contents

Protein chains

194 a.a. *

123 a.a. *

Ligands

GNP ×2

Metals

_MG ×2

Waters ×423

* Residue conservation analysis

PDB id:

1nf3

Name:

Signaling protein

Title:

Structure of cdc42 in a complex with the gtpase-binding domain of the cell polarity protein, par6

Structure:

G25k gtp-binding protein, placental isoform. Chain: a, b. Synonym: gp, cdc42 homolog. Engineered: yes. Mutation: yes. Par-6b. Chain: c, d. Fragment: gtpase-binding domain. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: cdc42. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Mus musculus. House mouse. Organism_taxid: 10090.

Biol. unit:

Tetramer (from PQS)

Resolution:

2.10Å R-factor: 0.219 R-free: 0.273

Authors:

S.M.Garrard,C.T.Capaldo,L.Gao,M.K.Rosen,I.G.Macara,D.R.Tomchick

Key ref:

S.M.Garrard et al. (2003). Structure of Cdc42 in a complex with the GTPase-binding domain of the cell polarity protein, Par6. EMBO J, 22, 1125-1133. PubMed id: 12606577 DOI: 10.1093/emboj/cdg110

Date:

12-Dec-02 Release date: 04-Mar-03

Protein chains

P60953  (CDC42_HUMAN) -  Cell division control protein 42 homolog from Homo sapiens

Seq: 191 a.a.

Struc: 194 a.a.*

Protein chains

Q9JK83  (PAR6B_MOUSE) -  Partitioning defective 6 homolog beta from Mus musculus

Seq: 371 a.a.

Struc: 123 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains A, B: E.C.3.6.5.2 - small monomeric GTPase.
• Reaction: GTP + H2O = GDP + phosphate + H⁺

GTP + H2O = GDP (Bound ligand (Het Group name = GNP) matches with 81.82% similarity) + phosphate + H(+)

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

reference

DOI no: 10.1093/emboj/cdg110

EMBO J 22:1125-1133 (2003)

PubMed id: 12606577

Structure of Cdc42 in a complex with the GTPase-binding domain of the cell polarity protein, Par6.

S.M.Garrard, C.T.Capaldo, L.Gao, M.K.Rosen, I.G.Macara, D.R.Tomchick.

ABSTRACT

Cdc42 is a small GTPase that is required for cell polarity establishment in eukaryotes as diverse as budding yeast and mammals. Par6 is also implicated in metazoan cell polarity establishment and asymmetric cell divisions. Cdc42.GTP interacts with proteins that contain a conserved sequence called a CRIB motif. Uniquely, Par6 possesses a semi-CRIB motif that is not sufficient for binding to Cdc42. An adjacent PDZ domain is also necessary and is required for biological effects of Par6. Here we report the crystal structure of a complex between Cdc42 and the Par6 GTPase-binding domain. The semi-CRIB motif forms a beta-strand that inserts between the four strands of Cdc42 and the three strands of the PDZ domain to form a continuous eight-stranded sheet. Cdc42 induces a conformational change in Par6, detectable by fluorescence resonance energy transfer spectroscopy. Nuclear magnetic resonance studies indicate that the semi-CRIB motif of Par6 is at least partially structured by the PDZ domain. The structure highlights a novel role for a PDZ domain as a structural scaffold.

Selected figure(s)

Figure 2.
Figure 2 Crystal structure of Par6B(126 -253) bound to Cdc42(Q61L) GMPPNP at 2.1 Å resolution. Ribbon diagram with Cdc42 colored blue and Par6 yellow (left and center images). A structure of the WASP -Cdc42 complex (Abdul-Manan et al., 1999) is also shown on the right, for comparison. The Switch I and II regions of Cdc42 are colored red, the semi-CRIB motif of Par6 and the CRIB motif of WASP are colored black, and the GMP-PNP/Mg2+(H[2]O)[2] moiety is presented in ball-and-stick representation. A short region of the PDZ domain of Par6 (residues 204 -208) that makes contact with Cdc42 is highlighted in magenta. The center image is of the complex rotated by 90° about the vertical axis. The black arrow indicates the location of the PDZ ligand-binding pocket.

Figure 6.
Figure 6 Overlaid 1H/15N HSQC spectra of the Par6 PDZ domain (residues 152 -253, red) and CRIB -PDZ elements (residues 126 -253, black).

The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2003, 22, 1125-1133) copyright 2003.

Figures were selected by an automated process.