2rmk › Citations

The Rac1 polybasic region is required for interaction with its effector PRK1.

Modha R, Campbell LJ, Nietlispach D, Buhecha HR, Owen D, Mott HR
J Biol Chem 283 1492-1500 (2008)
Cited: 38 times
EuropePMC logo PMID: 18006505

Abstract

Protein kinase C-related kinase 1 (PRK1 or PKN) is involved in regulation of the intermediate filaments of the actin cytoskeleton, as well as having effects on processes as diverse as mitotic timing and apoptosis. It is activated by interacting with the Rho family small G proteins and arachidonic acid or by caspase cleavage. We have previously shown that the HR1b of PRK1 binds exclusively to Rac1, whereas the HR1a domain binds to both Rac1 and RhoA. Here, we have determined the solution structure of the HR1b-Rac complex. We show that HR1b binds to the C-terminal end of the effector loop and switch 2 of Rac1. Comparison with the HR1a-RhoA structure shows that this part of the Rac1-HR1b interaction is homologous to one of the contact sites that HR1a makes with RhoA. The Rac1 used in this study included the C-terminal polybasic region, which is frequently omitted from structural studies, as well as the core G domain. The Rac1 C-terminal region reverses in direction to interact with residues in switch 2, and the polybasic region itself interacts with residues in HR1b. The interactions with HR1b do not prevent the polybasic region being available to contact the negatively charged membrane phospholipids, which is considered to be its primary role. This is the first structural demonstration that the C terminus of a G protein forms a novel recognition element for effector binding.

Articles - 2rmk mentioned but not cited (5)

  1. Structure of an SspH1-PKN1 complex reveals the basis for host substrate recognition and mechanism of activation for a bacterial E3 ubiquitin ligase. Keszei AF, Tang X, McCormick C, Zeqiraj E, Rohde JR, Tyers M, Sicheri F. Mol Cell Biol 34 362-373 (2014)
  2. Investigation of the Interaction between Cdc42 and Its Effector TOCA1: HANDOVER OF Cdc42 TO THE ACTIN REGULATOR N-WASP IS FACILITATED BY DIFFERENTIAL BINDING AFFINITIES. Watson JR, Fox HM, Nietlispach D, Gallop JL, Owen D, Mott HR. J Biol Chem 291 13875-13890 (2016)
  3. The interplay of Rac1 activity, ubiquitination and GDI binding and its consequences for endothelial cell spreading. Majolée J, Podieh F, Hordijk PL, Kovačević I. PLoS One 16 e0254386 (2021)
  4. Structural Basis of CYRI-B Direct Competition with Scar/WAVE Complex for Rac1. Yelland T, Le AH, Nikolaou S, Insall R, Machesky L, Ismail S. Structure 29 226-237.e4 (2021)
  5. The structure and function of protein kinase C-related kinases (PRKs). Sophocleous G, Owen D, Mott HR. Biochem Soc Trans 49 217-235 (2021)


Reviews citing this publication (7)

  1. Structures of Ras superfamily effector complexes: What have we learnt in two decades? Mott HR, Owen D. Crit Rev Biochem Mol Biol 50 85-133 (2015)
  2. Toward understanding RhoGTPase specificity: structure, function and local activation. Schaefer A, Reinhard NR, Hordijk PL. Small GTPases 5 6 (2014)
  3. The Rac1 hypervariable region in targeting and signaling: a tail of many stories. Lam BD, Hordijk PL. Small GTPases 4 78-89 (2013)
  4. Purine nucleosides: endogenous neuroprotectants in hypoxic brain. Thauerer B, Zur Nedden S, Baier-Bitterlich G. J Neurochem 121 329-342 (2012)
  5. PKC and PKN in heart disease. Marrocco V, Bogomolovas J, Ehler E, Dos Remedios CG, Yu J, Gao C, Lange S. J Mol Cell Cardiol 128 212-226 (2019)
  6. Cdc42 in actin dynamics: An ordered pathway governed by complex equilibria and directional effector handover. Watson JR, Owen D, Mott HR. Small GTPases 8 237-244 (2017)
  7. Allostery and dynamics in small G proteins. Mott HR, Owen D. Biochem Soc Trans 46 1333-1343 (2018)

Articles citing this publication (26)

  1. An allosteric kinase inhibitor binds the p21-activated kinase autoregulatory domain covalently. Viaud J, Peterson JR. Mol Cancer Ther 8 2559-2565 (2009)
  2. Distinct regions of the Pseudomonas syringae coiled-coil effector AvrRps4 are required for activation of immunity. Sohn KH, Hughes RK, Piquerez SJ, Jones JD, Banfield MJ. Proc Natl Acad Sci U S A 109 16371-16376 (2012)
  3. Compensatory and long-range changes in picosecond-nanosecond main-chain dynamics upon complex formation: 15N relaxation analysis of the free and bound states of the ubiquitin-like domain of human plexin-B1 and the small GTPase Rac1. Bouguet-Bonnet S, Buck M. J Mol Biol 377 1474-1487 (2008)
  4. Nuclear factor of activated T cells c1 mediates p21-activated kinase 1 activation in the modulation of chemokine-induced human aortic smooth muscle cell F-actin stress fiber formation, migration, and proliferation and injury-induced vascular wall remodeling. Kundumani-Sridharan V, Singh NK, Kumar S, Gadepalli R, Rao GN. J Biol Chem 288 22150-22162 (2013)
  5. The RalB-RLIP76 complex reveals a novel mode of ral-effector interaction. Fenwick RB, Campbell LJ, Rajasekar K, Prasannan S, Nietlispach D, Camonis J, Owen D, Mott HR. Structure 18 985-995 (2010)
  6. Mammalian target of rapamycin complex 2 regulates muscle glucose uptake during exercise in mice. Kleinert M, Parker BL, Fritzen AM, Knudsen JR, Jensen TE, Kjøbsted R, Sylow L, Ruegg M, James DE, Richter EA. J Physiol 595 4845-4855 (2017)
  7. Crucial roles of TNFAIP8 protein in regulating apoptosis and Listeria infection. Porturas TP, Sun H, Buchlis G, Lou Y, Liang X, Cathopoulis T, Fayngerts S, Johnson DS, Wang Z, Chen YH. J Immunol 194 5743-5750 (2015)
  8. Rac1 acts in conjunction with Nedd4 and dishevelled-1 to promote maturation of cell-cell contacts. Nethe M, de Kreuk BJ, Tauriello DV, Anthony EC, Snoek B, Stumpel T, Salinas PC, Maurice MM, Geerts D, Deelder AM, Hensbergen PJ, Hordijk PL. J Cell Sci 125 3430-3442 (2012)
  9. Combining NMR and molecular dynamics studies for insights into the allostery of small GTPase-protein interactions. Zhang L, Bouguet-Bonnet S, Buck M. Methods Mol Biol 796 235-259 (2012)
  10. Vital role of protein kinase C-related kinase in the formation and stability of neurites during hypoxia. Thauerer B, zur Nedden S, Baier-Bitterlich G. J Neurochem 113 432-446 (2010)
  11. Intracellular mature IL-37 suppresses tumor metastasis via inhibiting Rac1 activation. Li Y, Zhao M, Guo C, Chu H, Li W, Chen X, Wang X, Li Y, Jia Y, Koussatidjoa S, Zhu F, Wang J, Wang X, Wang Q, Zhao W, Shi Y, Chen W, Zhang L. Oncogene 37 1095-1106 (2018)
  12. The polybasic region of Rac1 modulates bacterial uptake independently of self-association and membrane targeting. Wong KW, Mohammadi S, Isberg RR. J Biol Chem 283 35954-35965 (2008)
  13. The polybasic region of Rho GTPases defines the cleavage by Yersinia enterocolitica outer protein T (YopT). Fueller F, Schmidt G. Protein Sci 17 1456-1462 (2008)
  14. Protein Kinase C-Related Kinase (PKN/PRK). Potential Key-Role for PKN1 in Protection of Hypoxic Neurons. Thauerer B, Zur Nedden S, Baier-Bitterlich G. Curr Neuropharmacol 12 213-218 (2014)
  15. RLIP76 (RalBP1): The first piece of the structural puzzle. Mott HR, Owen D. Small GTPases 1 157-160 (2010)
  16. Disruption of a RAC1-centred network is associated with Alzheimer's disease pathology and causes age-dependent neurodegeneration. Kikuchi M, Sekiya M, Hara N, Miyashita A, Kuwano R, Ikeuchi T, Iijima KM, Nakaya A. Hum Mol Genet 29 817-833 (2020)
  17. Polybasic RKKR motif in the linker region of lipid droplet (LD)-associated protein CIDEC inhibits LD fusion activity by interacting with acidic phospholipids. Wang J, Yan C, Xu C, Chua BT, Li P, Chen FJ. J Biol Chem 293 19330-19343 (2018)
  18. The NMR structure of the TC10- and Cdc42-interacting domain of CIP4. Kobashigawa Y, Kumeta H, Kanoh D, Inagaki F. J Biomol NMR 44 113-118 (2009)
  19. Optimization and stabilization of Rho small GTPase proteins for solution NMR studies: The case of Rnd1. Cao S, Buck M. Small GTPases 2 295-304 (2011)
  20. (1)H, (13)C and (15)N resonance assignments of the Cdc42-binding domain of TOCA1. Watson JR, Nietlispach D, Owen D, Mott HR. Biomol NMR Assign 10 407-411 (2016)
  21. 1H, 15N and 13C resonance assignments of the HR1c domain of PRK1, a protein kinase C-related kinase. Sophocleous G, Wood G, Owen D, Mott HR. Biomol NMR Assign 14 245-250 (2020)
  22. Analysis of Functional Domains in Rho5, the Yeast Homolog of Human Rac1 GTPase, in Oxidative Stress Response. Sterk C, Gräber L, Schmitz HP, Heinisch JJ. Int J Mol Sci 20 (2019)
  23. Backbone assignment and secondary structure of Rnd1, an unusual Rho family small GTPase. Cao S, Mao X, Liu D, Buck M. Biomol NMR Assign 7 121-128 (2013)
  24. Characterization of the novel cardiolipin binding regions identified on the protease and lipid activated PKC-related kinase 1. Lin JLJ. Protein Sci 28 1473-1486 (2019)
  25. Mechanistic Differences of Activation of Rac1P29S and Rac1A159V. Senyuz S, Jang H, Nussinov R, Keskin O, Gursoy A. J Phys Chem B 125 3790-3802 (2021)
  26. Protein kinase N1 promotes proliferation and invasion of liver cancer. Wang X, Ge Y, Shi M, Dai H, Liu W, Wang P. Exp Ther Med 21 651 (2021)


Quick links