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| <StructureSection load='' size='500' 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'> | | <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'> |
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Revision as of 09:03, 6 September 2018
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Function
Rho GTPase of higher vertebrates include RhoA, RhoB, RhoC, RhoD and RhoE. These 3 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]. 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[2].
Disease
Mutations in RhoA were identified in diffuse gastric cancer[3].
Relevance
RhoA is thought to be important in mediating vasoconstriction in the penis[4].
Structural highlights
The transition state complex of RhoA and RhoGAP contains GDP, AlF4 and Mg+2 ion[5]. AlF4 and Mg+2 ion binding site.
- ↑ 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
- ↑ 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
- ↑ 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
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3D structures of Rho GTPase
Updated on 06-September-2018
{"openlevels":0}
- RhoA
- RhoA complex with guanine nucleotide exchange factor
- 4xh9 – hRhoA (mutant) + guanine nucleotide exchange factor NET1
- 5jhg, 5jhh - hRhoA + guanine nucleotide exchange factor 11
- 3t06, 1xcg – hRhoA (mutant) + guanine nucleotide exchange factor 11
- 1lb1 – hRhoA (mutant) + guanine nucleotide exchange factor Dbs
- 3kz1 – hRhoA + guanine nucleotide exchange factor 11 + GSP
- 1x86 – hRhoA + guanine nucleotide exchange factor 12
- RhoA complex with Rho GTPase-activating protein
- 5irc – hRhoA + Rho GTPase-activating protein 20 + GDP
- 1ow3, 5m6x, 5m70 – hRhoA + Rho GTPase-activating protein 1 + GDP
- 3msx – hRhoA (mutant) + Rho GTPase-activating protein 35 + GDP
- RhoA complex with ADP-ribosyltransferase
- 4xsg – hRhoA (mutant) + ADP-ribosyltransferase + GTP
- 4xsh – hRhoA (mutant) + ADP-ribosyltransferase + GSP + NADH
- 5bwm – hRhoA (mutant) + ADP-ribosyltransferase + GDP + NADH
- RhoA other complexes
- 5fr2, 5fr1, 1cc0 – hRhoA + Rho GDP-dissociation inhibitor 1 + GDP
- 5hpy – hRhoA (mutant) + unconventional myosin-IXB + GDP
- 4xoi – hRhoA (mutant) + actin-binding protein anillin + GTP
- 4f38 – mRhoA + Rho GDP-dissociation inhibitor 1 + GPPNP
- 4d0n – hRhoA + A-kinase anchor protein 13 + GDP
- 3lw8, 3lwn, 3lxr – hRhoA + IpgB2 + GDP
- 1s1c – hRhoA + ROCKI + GNP
- 1cxz – hRhoA + Pkn/Prk1 + GSP
- 1tx4 – hRhoA + RhoGap + GDP
- 2rgn – hRhoA + guanine nucleotide-binding protein alpha-Q + RhoA/Rac/CDC42 exchange factor + GDP
- 5c2k – hRhoA/Rac GTPase-activating protein 1 + GDP
- 5jcp – hRhoA/ARAP3 + GDP
- RhoB
- RhoC
- 2gcn – hRhoC + GDP
- 2gco – hRhoC + GPPNP
- 2gcp – hRhoC + GSP
- 2gcn – hRhoC (mutant) + diaphanous protein homolog 1 + GMPPNP
- RhoD
- RhoE
- 1m7b – hRhoE + GTP
- 1gwn – mRhoE core domain + GTP
- 2v55 – hRhoE + ROCKI + GTP + ANP
- Miro1
- 5kso, 5ksp, 5ksy – hMiro1 C-terminal + GDP
- 5ksz – hMiro1 EF hand and kinase domain + GMPPCP
- 5kty, 5ku1 – hMiro1 EF hand and kinase domain + GDP
- Miro2
- 5kut – hMiro2 C-terminal + GDP
- Miro
- 4c0j, 4c0k – DmMiro – Drosophila melanogaster
- 4c0l – DmMiro + GDP
References
proteopedia link