Rho GTPase: Difference between revisions

Latest revision as of 10:30, 6 August 2024

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Human RhoA (magenta) complex with RhoGAP (cyan), GDP, AlF4 and Mg+2 ion (green) (PDB code 1tx4)

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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].
Miro2 regulates inter-mitochondrial communication along microtubules^[7].

Disease

Mutations in RhoA were identified in diffuse gastric cancer^[8].

Relevance

RhoA is thought to be important in mediating vasoconstriction in the penis^[9].

Structural highlights

The transition state complex of RhoA and RhoGAP contains GDP, AlF4 and Mg+2 ion^[10]. Water molecules are shown as red spheres.

3D structures of Rho GTPase

Rho GTPase 3D structures

↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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:https://dx.doi.org/10.1074/jbc.M208609200
↑ Cao Y, Xu C, Ye J, He Q, Zhang X, Jia S, Qiao X, Zhang C, Liu R, Weng L, Liu Y, Liu L, Zheng M. Miro2 Regulates Inter-Mitochondrial Communication in the Heart and Protects Against TAC-Induced Cardiac Dysfunction. Circ Res. 2019 Sep 27;125(8):728-743. PMID:31455181 doi:10.1161/CIRCRESAHA.119.315432
↑ 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:https://dx.doi.org/10.1016/j.ccr.2014.06.022
↑ 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:https://dx.doi.org/10.1042/CS20050255
↑ 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

References

Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky, Joel L. Sussman

[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:https://dx.doi.org/10.1074/jbc.M208609200

[7] Cao Y, Xu C, Ye J, He Q, Zhang X, Jia S, Qiao X, Zhang C, Liu R, Weng L, Liu Y, Liu L, Zheng M. Miro2 Regulates Inter-Mitochondrial Communication in the Heart and Protects Against TAC-Induced Cardiac Dysfunction. Circ Res. 2019 Sep 27;125(8):728-743. PMID:31455181 doi:10.1161/CIRCRESAHA.119.315432

[8] 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:https://dx.doi.org/10.1016/j.ccr.2014.06.022

[9] 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:https://dx.doi.org/10.1042/CS20050255

[10] 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

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@@ Line 1: / Line 1: @@
-<StructureSection load='5c4m' size='340' side='right' caption='Caption for this structure' scene=''>
+<StructureSection load='' size='350' side='right' caption='Human RhoA (magenta) complex with RhoGAP (cyan), GDP, AlF4 and Mg+2 ion (green) (PDB code [[1tx4]])' scene='75/752220/Cv/1' pspeed='8'>
 == Function ==
-'''Rho GTPase''' of higher vertebrates include '''RhoA, RhoB''' and '''RhoC'''.  These 3 proteins share 85% sequence identity.  RhoA is the more extensively studied among these three. RhoA regulates a signal transduction pathway linking plasma membrane receptors to the assembly of focal adhesions and actin stress fibers.  A number of proteins have been identified as targets of RhoA<ref>PMID:12642488</ref>.
+'''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<ref>PMID:12642488</ref>.
+*'''RhoB''' has a role in actin organisation, membrane trafficking, cell proliferation, DNA repair and apoptosis<ref>PMID:27875099</ref>.
+*'''RhoD''' participates in regulating cell-cycle progression and centrosome duplication<ref>PMID:22665057</ref>.
+*'''RhoE''' induces loss of stress fibres and inhibits cell cycle progression<ref>PMID:16042565</ref>.
+*'''RhoG''' regulates actin-cytoskeleton dynamics, survival and proliferation in immune cells<ref>PMID:37378671</ref>.
+* '''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<ref>PMID:12482879</ref>.
+*'''Miro2''' regulates inter-mitochondrial communication along microtubules<ref>PMID:31455181</ref>.
 == Disease ==
@@ Line 12: / Line 18: @@
 == Structural highlights ==
+The <scene name='75/752220/Cv/6'>transition state complex of RhoA and RhoGAP contains GDP, AlF4 and Mg+2 ion</scene><ref>PMID:9338791</ref>. Water molecules are shown as red spheres.
+*<scene name='75/752220/Cv/7'>GDP binding site</scene>
+*<scene name='75/752220/Cv/8'>AlF4 and Mg+2 ion binding site</scene>.
+==3D structures of Rho GTPase==
+[[Rho GTPase 3D structures]]
 </StructureSection>
-==3D structures of Rho GTPase==
-Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
-{{#tree:id=OrganizedByTopic|openlevels=0|
-*RhoA
-**[[5ez6]], [[5c4m]], [[5a0f]], [[1dpf]], [[1ftn]] – hRhoA + GDP – human<br />
-**[[1kmq]] – hRhoA (mutant) + GNP<br />
-**[[1a2b]] – hRhoA + GSP<br />
-**[[3tvd]] – mRhoA + GSP – mouse<br />
-*RhoA complex with guanine nucleotide exchange factor
-**[[4xh9]] – hRhoA (mutant) + guanine nucleotide exchange factor NET1<br />
-**[[3t06]], [[1xcg]] – hRhoA (mutant) + guanine nucleotide exchange factor 11<br />
-**[[1lb1]] – hRhoA (mutant) + guanine nucleotide exchange factor Dbs<br />
-**[[3kz1]] – hRhoA + guanine nucleotide exchange factor 11 + GSP<br />
-**[[1x86]] – hRhoA + guanine nucleotide exchange factor 12<br />
-*RhoA complex with Rho GTPase-activating protein
-**[[5irc]] – hRhoA + Rho GTPase-activating protein 20 + GDP <br />
-**[[1ow3]] – hRhoA + Rho GTPase-activating protein 1 + GDP <br />
-**[[3msx]] – hRhoA (mutant) + Rho GTPase-activating protein 35 + GDP <br />
-*RhoA complex with ADP-ribosyltransferase
-**[[4xsg]] – hRhoA (mutant) + ADP-ribosyltransferase + GTP <br />
-**[[4xsh]] – hRhoA (mutant) + ADP-ribosyltransferase + GSP + NADH<br />
-**[[5bwm]] – hRhoA (mutant) + ADP-ribosyltransferase + GDP + NADH<br />
-*RhoA other complexes
-**[[5fr2]], [[5fr1]], [[1cc0]] – hRhoA + Rho GDP-dissociation inhibitor 1 + GDP <br />
-**[[5hpy]] – hRhoA (mutant) + unconventional myosin-IXB + GDP <br />
-**[[4xoi]] – hRhoA (mutant) + actin-binding protein anillin + GTP <br />
-**[[4f38]] – mRhoA + Rho GDP-dissociation inhibitor 1 + GPPNP <br />
-**[[4d0n]] – hRhoA + A-kinase anchor protein 13 + GDP<br />
-**[[3lw8]], [[3lwn]], [[3lxr]] – hRhoA + IpgB2 + GDP<br />
-**[[1s1c]] – hRhoA + ROCKI + GNP<br />
-**[[1cxz]] – hRhoA + Pkn/Prk1 + GSP<br />
-**[[1tx4]] – hRhoA + RhoGap + GDP<br />
-**[[2rgn]] – hRhoA + guanine nucleotide-binding protein alpha-Q + RhoA/Rac/CDC42 exchange factor + GDP<br />
-**[[5c2k]] – hRhoA/Rac GTPase-activating protein 1 + GDP <br />
-**[[5jcp]] – hRhoA/ARAP3 + GDP <br />
-*RhoB
-**[[2fv8]] – hRhoB + GDP <br />
-*RhoC
-**[[2gcn]] – hRhoC + GDP <br />
-**[[2gco]] – hRhoC + GPPNP <br />
-**[[2gcp]] – hRhoC + GSP <br />
-**[[2gcn]] – hRhoC (mutant) + diaphanous protein homolog 1 + GMPPNP <br />
-}}
 == References ==
 <references/>
+[[Category:Topic Page]]

Rho GTPase: Difference between revisions

Latest revision as of 10:30, 6 August 2024

Contents

Function

Disease

Relevance

Structural highlights

3D structures of Rho GTPase

References

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