4f38

From Proteopedia

(Difference between revisions)

Revision as of 04:31, 7 October 2022

Crystal structure of geranylgeranylated RhoA in complex with RhoGDI in its active GPPNHP-bound form

Structural highlights

4f38 is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RHOA_MOUSE Small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state (PubMed:14697203). Mainly associated with cytoskeleton organization, in active state binds to a variety of effector proteins to regulate cellular responses such as cytoskeletal dynamics, cell migration and cell cycle. Regulates a signal transduction pathway linking plasma membrane receptors to the assembly of focal adhesions and actin stress fibers. Involved in a microtubule-dependent signal that is required for the myosin contractile ring formation during cell cycle cytokinesis (By similarity). Plays an essential role in cleavage furrow formation. Required for the apical junction formation of keratinocyte cell-cell adhesion (PubMed:11777936, PubMed:20974804). Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. The MEMO1-RHOA-DIAPH1 signaling pathway plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. It controls the localization of APC and CLASP2 to the cell membrane, via the regulation of GSK3B activity. In turn, membrane-bound APC allows the localization of the MACF1 to the cell membrane, which is required for microtubule capture and stabilization (By similarity). Regulates KCNA2 potassium channel activity by reducing its location at the cell surface in response to CHRM1 activation; promotes KCNA2 endocytosis. Acts as an allosteric activator of guanine nucleotide exchange factor ECT2 by binding in its activated GTP-bound form to the PH domain of ECT2 which stimulates the release of PH inhibition and promotes the binding of substrate RHOA to the ECT2 catalytic center (By similarity). May be an activator of PLCE1 (PubMed:9635436). In neurons, involved in the inhibition of the initial spine growth. Upon activation by CaMKII, modulates dendritic spine structural plasticity by relaying CaMKII transient activation to synapse-specific, long-term signaling (By similarity). Acts as a regulator of platelet alpha-granule release during activation and aggregation of platelets (PubMed:14697203).[UniProtKB:P61586][UniProtKB:P61589]^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Small GTPases of the Rho family regulate cytoskeleton remodeling, cell polarity, and transcription, as well as the cell cycle, in eukaryotic cells. Membrane delivery and recycling of the Rho GTPases is mediated by Rho GDP dissociation inhibitor (RhoGDI), which forms a stable complex with prenylated Rho GTPases. We analyzed the interaction of RhoGDI with the active and inactive forms of prenylated and unprenylated RhoA. We demonstrate that RhoGDI binds the prenylated form of RhoA.GDP with unexpectedly high affinity (K(d) = 5 pm). The very long half-life of the complex is reduced 25-fold on RhoA activation, with a concomitant reduction in affinity (K(d) = 3 nm). The 2.8-A structure of the RhoA.guanosine 5'-[beta,gamma-imido] triphosphate (GMPPNP).RhoGDI complex demonstrated that complex formation forces the activated RhoA into a GDP-bound conformation in the absence of nucleotide hydrolysis. We demonstrate that membrane extraction of Rho GTPase by RhoGDI is a thermodynamically favored passive process that operates through a series of progressively tighter intermediates, much like the one that is mediated by RabGDI.

Quantitative Analysis of Prenylated RhoA Interaction with Its Chaperone, RhoGDI.,Tnimov Z, Guo Z, Gambin Y, Nguyen UT, Wu YW, Abankwa D, Stigter A, Collins BM, Waldmann H, Goody RS, Alexandrov K J Biol Chem. 2012 Aug 3;287(32):26549-62. Epub 2012 May 24. PMID:22628549^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Calautti E, Grossi M, Mammucari C, Aoyama Y, Pirro M, Ono Y, Li J, Dotto GP. Fyn tyrosine kinase is a downstream mediator of Rho/PRK2 function in keratinocyte cell-cell adhesion. J Cell Biol. 2002 Jan 7;156(1):137-48. Epub 2002 Jan 3. PMID:11777936 doi:http://dx.doi.org/10.1083/jcb.200105140
↑ Walther DJ, Peter JU, Winter S, Holtje M, Paulmann N, Grohmann M, Vowinckel J, Alamo-Bethencourt V, Wilhelm CS, Ahnert-Hilger G, Bader M. Serotonylation of small GTPases is a signal transduction pathway that triggers platelet alpha-granule release. Cell. 2003 Dec 26;115(7):851-62. doi: 10.1016/s0092-8674(03)01014-6. PMID:14697203 doi:http://dx.doi.org/10.1016/s0092-8674(03)01014-6
↑ Wallace SW, Magalhaes A, Hall A. The Rho target PRK2 regulates apical junction formation in human bronchial epithelial cells. Mol Cell Biol. 2011 Jan;31(1):81-91. doi: 10.1128/MCB.01001-10. Epub 2010 Oct 25. PMID:20974804 doi:10.1128/MCB.01001-10
↑ Cachero TG, Morielli AD, Peralta EG. The small GTP-binding protein RhoA regulates a delayed rectifier potassium channel. Cell. 1998 Jun 12;93(6):1077-85. doi: 10.1016/s0092-8674(00)81212-x. PMID:9635436 doi:http://dx.doi.org/10.1016/s0092-8674(00)81212-x
↑ Tnimov Z, Guo Z, Gambin Y, Nguyen UT, Wu YW, Abankwa D, Stigter A, Collins BM, Waldmann H, Goody RS, Alexandrov K. Quantitative Analysis of Prenylated RhoA Interaction with Its Chaperone, RhoGDI. J Biol Chem. 2012 Aug 3;287(32):26549-62. Epub 2012 May 24. PMID:22628549 doi:10.1074/jbc.M112.371294

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4f38"

Categories: Large Structures | Mus musculus | Alexandrov K | Guo Z | Tnimov Z

@@ Line 1: / Line 1: @@
 ==Crystal structure of geranylgeranylated RhoA in complex with RhoGDI in its active GPPNHP-bound form==
-<StructureSection load='4f38' size='340' side='right' caption='[[4f38]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
+<StructureSection load='4f38' size='340' side='right'caption='[[4f38]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4f38]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4F38 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4F38 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4f38]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4F38 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4F38 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GER:GERAN-8-YL+GERAN'>GER</scene>, <scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GER:GERAN-8-YL+GERAN'>GER</scene>, <scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Rhoa, Arha, Arha2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Arhgdia, C87222, Gdi1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4f38 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f38 OCA], [https://pdbe.org/4f38 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4f38 RCSB], [https://www.ebi.ac.uk/pdbsum/4f38 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4f38 ProSAT]</span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4f38 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f38 OCA], [http://pdbe.org/4f38 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4f38 RCSB], [http://www.ebi.ac.uk/pdbsum/4f38 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4f38 ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/RHOA_MOUSE RHOA_MOUSE] Small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state (PubMed:14697203). Mainly associated with cytoskeleton organization, in active state binds to a variety of effector proteins to regulate cellular responses such as cytoskeletal dynamics, cell migration and cell cycle. Regulates a signal transduction pathway linking plasma membrane receptors to the assembly of focal adhesions and actin stress fibers. Involved in a microtubule-dependent signal that is required for the myosin contractile ring formation during cell cycle cytokinesis (By similarity). Plays an essential role in cleavage furrow formation. Required for the apical junction formation of keratinocyte cell-cell adhesion (PubMed:11777936, PubMed:20974804). Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. The MEMO1-RHOA-DIAPH1 signaling pathway plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. It controls the localization of APC and CLASP2 to the cell membrane, via the regulation of GSK3B activity. In turn, membrane-bound APC allows the localization of the MACF1 to the cell membrane, which is required for microtubule capture and stabilization (By similarity). Regulates KCNA2 potassium channel activity by reducing its location at the cell surface in response to CHRM1 activation; promotes KCNA2 endocytosis. Acts as an allosteric activator of guanine nucleotide exchange factor ECT2 by binding in its activated GTP-bound form to the PH domain of ECT2 which stimulates the release of PH inhibition and promotes the binding of substrate RHOA to the ECT2 catalytic center (By similarity). May be an activator of PLCE1 (PubMed:9635436). In neurons, involved in the inhibition of the initial spine growth. Upon activation by CaMKII, modulates dendritic spine structural plasticity by relaying CaMKII transient activation to synapse-specific, long-term signaling (By similarity). Acts as a regulator of platelet alpha-granule release during activation and aggregation of platelets (PubMed:14697203).[UniProtKB:P61586][UniProtKB:P61589]<ref>PMID:11777936</ref> <ref>PMID:14697203</ref> <ref>PMID:20974804</ref> <ref>PMID:9635436</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 20: / Line 21: @@
 ==See Also==
 *[[Guanine nucleotide dissociation inhibitor|Guanine nucleotide dissociation inhibitor]]
+*[[Rho GTPase 3D structures|Rho GTPase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Lk3 transgenic mice]]
+[[Category: Large Structures]]
-[[Category: Alexandrov, K]]
+[[Category: Mus musculus]]
-[[Category: Guo, Z]]
+[[Category: Alexandrov K]]
-[[Category: Tnimov, Z]]
+[[Category: Guo Z]]
-[[Category: Active gppnhp bound form]]
+[[Category: Tnimov Z]]
-[[Category: Cell cycle-chaperone complex]]
-[[Category: Rhoa]]
-[[Category: Rhogdi]]

4f38

From Proteopedia

Revision as of 04:31, 7 October 2022

Crystal structure of geranylgeranylated RhoA in complex with RhoGDI in its active GPPNHP-bound form

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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