1hh4
From Proteopedia
| Line 4: | Line 4: | ||
==Overview== | ==Overview== | ||
| - | A heterodimer of prenylated Rac1 and Rho GDP dissociation inhibitor was | + | 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. |
==About this Structure== | ==About this Structure== | ||
| Line 13: | Line 13: | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Dagher, M | + | [[Category: Dagher, M C.]] |
[[Category: Faure, J.]] | [[Category: Faure, J.]] | ||
[[Category: Fieschi, F.]] | [[Category: Fieschi, F.]] | ||
[[Category: Grizot, S.]] | [[Category: Grizot, S.]] | ||
[[Category: Pebay-Peyroula, E.]] | [[Category: Pebay-Peyroula, E.]] | ||
| - | [[Category: Vignais, P | + | [[Category: Vignais, P V.]] |
[[Category: GDP]] | [[Category: GDP]] | ||
[[Category: GER]] | [[Category: GER]] | ||
| Line 28: | Line 28: | ||
[[Category: small g protein]] | [[Category: small g protein]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:01:11 2008'' |
Revision as of 11:01, 21 February 2008
|
RAC1-RHOGDI COMPLEX INVOLVED IN NADPH OXIDASE ACTIVATION
Overview
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.
About this Structure
1HH4 is a Protein complex structure of sequences from Homo sapiens with , and as ligands. Known structural/functional Sites: , , and . Full crystallographic information is available from OCA.
Reference
Crystal structure of the Rac1-RhoGDI complex involved in nadph oxidase activation., Grizot S, Faure J, Fieschi F, Vignais PV, Dagher MC, Pebay-Peyroula E, Biochemistry. 2001 Aug 28;40(34):10007-13. PMID:11513578
Page seeded by OCA on Thu Feb 21 13:01:11 2008
Categories: Homo sapiens | Protein complex | Dagher, M C. | Faure, J. | Fieschi, F. | Grizot, S. | Pebay-Peyroula, E. | Vignais, P V. | GDP | GER | MG | Gtp-binding | Gtpase activation | Lipoprotein | Prenylation | Small g protein
