Rho GTPase

From Proteopedia

Revision as of 10:21, 6 August 2024

spinqualitylabelsall models Human RhoA (magenta) complex with RhoGAP (cyan), GDP, AlF4 and Mg+2 ion (green) (PDB code 1tx4) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image Contents 1 Function 2 Disease 3 Relevance 4 Structural highlights 5 3D structures of Rho GTPase Function Rho GTPase or Rho-related GTP-binding protein of higher vertebrates include RhoA, RhoB, RhoC, RhoD and RhoE. These proteins share 85% sequence identity. RhoA is the more extensively studied among these three. RhoA regulates a signal transduction phosphorylation pathway linking plasma membrane receptors to the assembly of focal adhesions and actin stress fibers. Rho GTPase operates as a switch cycling between the active GTP-bound form and the inactive GDP-bound one. A number of proteins have been identified as targets of RhoA[1]. RhoB has a role in actin organisation, membrane trafficking, cell proliferation, DNA repair and apoptosis[2]. RhoD participates in regulating cell-cycle progression and centrosome duplication[3]. RhoE induces loss of stress fibres and inhibits cell cycle progression[4]. RhoG regulates actin-cytoskeleton dynamics, survival and proliferation in immune cells[5]. Mitochondrial Rho GTPase (Miro) have tandem GTP-binding domains separated by a linker region containing calcium-binding EF hand motifs indicating a role in mitochondrial homeostasis and apoptosis[6]. Disease Mutations in RhoA were identified in diffuse gastric cancer[7]. Relevance RhoA is thought to be important in mediating vasoconstriction in the penis[8]. Structural highlights The [9]. Water molecules are shown as red spheres. . 3D structures of Rho GTPase Rho GTPase 3D structures

References

1. ↑ Sepp KJ, Auld VJ. RhoA and Rac1 GTPases mediate the dynamic rearrangement of actin in peripheral glia. Development. 2003 May;130(9):1825-35. PMID:12642488
2. ↑ Vega FM, Ridley AJ. The RhoB small GTPase in physiology and disease. Small GTPases. 2018 Sep 3;9(5):384-393. PMID:27875099 doi:10.1080/21541248.2016.1253528
3. ↑ Kyrkou A, Soufi M, Bahtz R, Ferguson C, Bai M, Parton RG, Hoffmann I, Zerial M, Fotsis T, Murphy C. RhoD participates in the regulation of cell-cycle progression and centrosome duplication. Oncogene. 2013 Apr 4;32(14):1831-42. PMID:22665057 doi:10.1038/onc.2012.195
4. ↑ Riento K, Villalonga P, Garg R, Ridley A. Function and regulation of RhoE. Biochem Soc Trans. 2005 Aug;33(Pt 4):649-51. PMID:16042565 doi:10.1042/BST0330649
5. ↑ Rai SK, Singh D, Sarangi PP. Role of RhoG as a regulator of cellular functions: integrating insights on immune cell activation, migration, and functions. Inflamm Res. 2023 Jul;72(7):1453-1463. PMID:37378671 doi:10.1007/s00011-023-01761-9
6. ↑ Fransson A, Ruusala A, Aspenstrom P. Atypical Rho GTPases have roles in mitochondrial homeostasis and apoptosis. J Biol Chem. 2003 Feb 21;278(8):6495-502. Epub 2002 Dec 12. PMID:12482879 doi:http://dx.doi.org/10.1074/jbc.M208609200
7. ↑ Zhou J, Hayakawa Y, Wang TC, Bass AJ. RhoA mutations identified in diffuse gastric cancer. Cancer Cell. 2014 Jul 14;26(1):9-11. doi: 10.1016/j.ccr.2014.06.022. PMID:25026207 doi:http://dx.doi.org/10.1016/j.ccr.2014.06.022
8. ↑ Jin L, Burnett AL. RhoA/Rho-kinase in erectile tissue: mechanisms of disease and therapeutic insights. Clin Sci (Lond). 2006 Feb;110(2):153-65. PMID:16411892 doi:http://dx.doi.org/10.1042/CS20050255
9. ↑ Rittinger K, Walker PA, Eccleston JF, Smerdon SJ, Gamblin SJ. Structure at 1.65 A of RhoA and its GTPase-activating protein in complex with a transition-state analogue. Nature. 1997 Oct 16;389(6652):758-62. PMID:9338791 doi:10.1038/39651