PDBsum entry 1cc0

Signaling protein

PDB id: 1cc0

Contents

Protein chains

187 a.a. *

180 a.a. *

Ligands

GDP ×2

Metals

_MG ×2

* Residue conservation analysis

PDB id:

1cc0

Name:

Signaling protein

Title:

Crystal structure of the rhoa.Gdp-rhogdi complex

Structure:

Transforming protein rhoa. Chain: a, c. Synonym: gtp-binding protein rhoa, gtpase rhoa. Engineered: yes. Rho gdp dissociation inhibitor alpha. Chain: e, f. Synonym: rho gdi 1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Cellular_location: cytoplasm. Expressed in: saccharomyces cerevisiae. Expression_system_taxid: 4932. Other_details: coexpression with rhogdi. Other_details: coexpression with rhoa

Biol. unit:

Octamer (from PQS)

Resolution:

5.00Å R-factor: not given

Authors:

K.L.Longenecker,P.Read,U.Derewenda,Z.Dauter,S.Garrard,L.Walker, A.V.Somlyo,A.P.Somlyo,R.K.Nakamoto,Z.S.Derewenda

Key ref:

K.Longenecker et al. (1999). How RhoGDI binds Rho. Acta Crystallogr D Biol Crystallogr, 55, 1503-1515. PubMed id: 10489445 DOI: 10.1107/S090744499900801X

Date:

03-Mar-99 Release date: 07-Jan-00

Protein chains

P61586  (RHOA_HUMAN) -  Transforming protein RhoA from Homo sapiens

Seq: 193 a.a.

Struc: 187 a.a.*

Protein chains

P52565  (GDIR1_HUMAN) -  Rho GDP-dissociation inhibitor 1 from Homo sapiens

Seq: 204 a.a.

Struc: 180 a.a.

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

Enzyme reactions

• Enzyme class 2: Chains A, C: E.C.3.6.5.2 - small monomeric GTPase.
• Reaction: GTP + H2O = GDP + phosphate + H⁺

GTP + H2O = GDP (Bound ligand (Het Group name = GDP) corresponds exactly) + phosphate + H(+)

• Enzyme class 3: Chains E, F: E.C.?

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

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

reference

DOI no: 10.1107/S090744499900801X

Acta Crystallogr D Biol Crystallogr 55:1503-1515 (1999)

PubMed id: 10489445

How RhoGDI binds Rho.

K.Longenecker, P.Read, U.Derewenda, Z.Dauter, X.Liu, S.Garrard, L.Walker, A.V.Somlyo, R.K.Nakamoto, A.P.Somlyo, Z.S.Derewenda.

ABSTRACT

Like all Rho (Ras homology) GTPases, RhoA functions as a molecular switch in cell signaling, alternating between GTP- and GDP-bound states, with its biologically inactive GDP-bound form maintained as a cytosolic complex with RhoGDI (guanine nucleotide-exchange inhibitor). The crystal structures of RhoA-GDP and of the C-terminal immunoglobulin-like domain of RhoGDI (residues 67-203) are known, but the mechanism by which the two proteins interact is not known. The functional human RhoA-RhoGDI complex has been expressed in yeast and crystallized (P6(5)22, unit-cell parameters a = b = 139, c = 253 A, two complexes in the asymmetric unit). Although diffraction from these crystals extends to 3.5 A and is highly anisotropic, the experimentally phased (MAD plus MIR) electron-density map was adequate to reveal the mutual disposition of the two molecules. The result was validated by molecular-replacement calculations when data were corrected for anisotropy. Furthermore, the N-terminus of RhoGDI (the region involved in inhibition of nucleotide exchange) can be identified in the electron-density map: it is bound to the switch I and switch II regions of RhoA, occluding an epitope which binds Dbl-like nucleotide-exchange factors. The entrance of the hydrophobic pocket of RhoGDI is 25 A from the last residue in the RhoA model, with its C-terminus oriented to accommodate the geranylgeranyl group without conformational change in RhoA.

Selected figure(s)

Figure 8.
Figure 8 Model of the complex with the N-terminal fragment of RhoGDI. A model which follows the residual density is highlighted in orange and is shown from the same view as in Fig. 7-.

Figure 10.
Figure 10 Amino-acid sequence conservation is represented on the surface of RhoA as a gradation from gray to dark blue, corresponding to 100% conservation [figure prepared using GRASP with modifications as described by Soisson et al. (1998[Soisson, S. M., Nimnual, A. S., Uy, M., Bar-Sagi, D. & Kuriyan, J. (1998). Cell, 95, 259-268.])].

The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (1999, 55, 1503-1515) copyright 1999.

Figures were selected by the author.