1HH4

Rac1-RhoGDI complex involved in NADPH oxidase activation

Summary for 1HH4

• Entry DOI: 10.2210/pdb1hh4/pdb
• Related: 1CC0 1E96 1HE1 1MH1 1RHO
• NMR Information: BMRB: 5511
• Descriptor: RAS-RELATED C3 BOTULINUM TOXIN SUBSTRATE 1, RHO GDP-DISSOCIATION INHIBITOR 1, GUANOSINE-5'-DIPHOSPHATE, ... (6 entities in total)
• Functional Keywords: signaling protein/inhibitor, singal protein inhibitor complex, small g protein, gtpase activation, gtp-binding, prenylation, lipoprotein, signaling protein-inhibitor complex
• Biological source: HOMO SAPIENS (HUMAN); More
• Total number of polymer chains: 4
• Total formula weight: 90728.04

Authors

Grizot, S.,Faure, J.,Fieschi, F.,Vignais, P.V.,Dagher, M.-C.,Pebay-Peyroula, E. (deposition date: 2000-12-20, release date: 2001-08-28, Last modification date: 2023-12-13)

Primary citation

Grizot, S.,Faure, J.,Fieschi, F.,Vignais, P.V.,Dagher, M.-C.,Pebay-Peyroula, E.
Crystal Structure of the Rac1-Rhogdi Complex Involved in Nadph Oxidase Activation
Biochemistry, 40:10007-, 2001

PubMed Abstract: A heterodimer of prenylated Rac1 and Rho GDP dissociation inhibitor was purified and found to be competent in NADPH oxidase activation. Small angle neutron scattering experiments confirmed a 1:1 stoichiometry. The crystal structure of the Rac1-RhoGDI complex was determined at 2.7 A resolution. In this complex in which Rac1 is bound to GDP, the switch I region of Rac1 is in the GDP conformation whereas the switch II region resembles that of a GTP-bound GTPase. Two types of interaction between RhoGTPases and RhoGDI were investigated. The lipid-protein interaction between the geranylgeranyl moiety of Rac1 and RhoGDI resulted in numerous structural changes in the core of RhoGDI. The interactions between Rac1 and RhoGDI occur through hydrogen bonds which involve a number of residues of Rac1, namely, Tyr64(Rac), Arg66(Rac), His103(Rac), and His104(Rac), conserved within the Rho family and localized in the switch II region or in its close neighborhood. Moreover, in the switch II region of Rac1, hydrophobic interactions involving Leu67(Rac) and Leu70(Rac) contribute to the stability of the Rac1-RhoGDI complex. Inhibition of the GDP-GTP exchange in Rac1 upon binding to RhoGDI partly results from interaction of Thr35(Rac) with Asp45(GDI). In the Rac1-RhoGDI complex, the accessibility of the effector loops of Rac1 probably accounts for the ability of the Rac1-RhoGDI complex to activate the NADPH oxidase.

PubMed: 11513578
DOI: 10.1021/BI010288K

Experimental method

X-RAY DIFFRACTION (2.7 Å)