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3eg5

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Revision as of 22:02, 2 December 2018

Crystal structure of MDIA1-TSH GBD-FH3 in complex with CDC42-GMPPNP

Structural highlights

3eg5 is a 4 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	1z2c, 2bap
Gene:	Cdc42 (LK3 transgenic mice), Diaph1 (LK3 transgenic mice)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[CDC42_MOUSE] Plasma membrane-associated small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state. In active state binds to a variety of effector proteins to regulate cellular responses. Involved in epithelial cell polarization processes. Regulates the bipolar attachment of spindle microtubules to kinetochores before chromosome congression in metaphase. Plays a role in the extension and maintenance of the formation of thin, actin-rich surface projections called filopodia. Mediates CDC42-dependent cell migration. [DIAP1_MOUSE] Acts in a Rho-dependent manner to recruit PFY1 to the membrane. Required for the assembly of F-actin structures, such as actin cables and stress fibers. Nucleates actin filaments. Binds to the barbed end of the actin filament and slows down actin polymerization and depolymerization. Required for cytokinesis, and transcriptional activation of the serum response factor. DFR proteins couple Rho and Src tyrosine kinase during signaling and the regulation of actin dynamics. Functions as a scaffold protein for MAPRE1 and APC to stabilize microtubules and promote cell migration. Has neurite outgrowth promoting activity. 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. Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape (By similarity).^[1] ^[2] ^[3] ^[4]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Formins are key regulators of actin nucleation and polymerization. They contain formin homology 1 (FH1) and 2 (FH2) domains as the catalytic machinery for the formation of linear actin cables. A subclass of formins constitutes the Diaphanous-related formins, members of which are regulated by the binding of a small GTP-binding protein of the Rho subfamily. Binding of these molecular switch proteins to the regulatory N-terminal mDia(N), including the GTPase-binding domain, leads to the release of auto-inhibition. From the three mDia isoforms, mDia1 is activated only by Rho (RhoA, -B, and -C), in contrast to mDia2 and -3, which is also activated by Rac and Cdc42. Little is known about the determinants of specificity. Here we report on the interactions of RhoA, Rac1, and Cdc42 with mDia1 and an mDia1 mutant (mDia(N)-Thr-Ser-His (TSH)), which based on structural information should mimic mDia2 and -3. Specificity is analyzed by biochemical studies and a structural analysis of a complex between Cdc42.Gpp(NH)p and mDia(N)-TSH. A triple NNN motif in mDia1 (amino acids 164-166), corresponding to the TSH motif in mDia2/3 (amino acids 183-185 and 190-192), and the epitope interacting with the Rho insert helix are essential for high affinity binding. The triple N motif of mDia1 allows tight interaction with Rho because of the presence of Phe-106, whereas the corresponding His-104 in Rac and Cdc42 forms a complementary interface with the TSH motif in mDia2/3. We also show that the F106H and H104F mutations drastically alter the affinities and thermodynamics of mDia interactions.

Specificity of interactions between mDia isoforms and Rho proteins.,Lammers M, Meyer S, Kuhlmann D, Wittinghofer A J Biol Chem. 2008 Dec 12;283(50):35236-46. Epub 2008 Sep 30. PMID:18829452^[5]

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

References

↑ Watanabe N, Madaule P, Reid T, Ishizaki T, Watanabe G, Kakizuka A, Saito Y, Nakao K, Jockusch BM, Narumiya S. p140mDia, a mammalian homolog of Drosophila diaphanous, is a target protein for Rho small GTPase and is a ligand for profilin. EMBO J. 1997 Jun 2;16(11):3044-56. PMID:9214622 doi:http://dx.doi.org/10.1093/emboj/16.11.3044
↑ Tominaga T, Sahai E, Chardin P, McCormick F, Courtneidge SA, Alberts AS. Diaphanous-related formins bridge Rho GTPase and Src tyrosine kinase signaling. Mol Cell. 2000 Jan;5(1):13-25. PMID:10678165
↑ Higashida C, Miyoshi T, Fujita A, Oceguera-Yanez F, Monypenny J, Andou Y, Narumiya S, Watanabe N. Actin polymerization-driven molecular movement of mDia1 in living cells. Science. 2004 Mar 26;303(5666):2007-10. PMID:15044801 doi:http://dx.doi.org/10.1126/science.1093923
↑ Schwaibold EM, Brandt DT. Identification of Neurochondrin as a new interaction partner of the FH3 domain of the Diaphanous-related formin Dia1. Biochem Biophys Res Commun. 2008 Aug 29;373(3):366-72. doi:, 10.1016/j.bbrc.2008.06.042. Epub 2008 Jun 20. PMID:18572016 doi:http://dx.doi.org/10.1016/j.bbrc.2008.06.042
↑ Lammers M, Meyer S, Kuhlmann D, Wittinghofer A. Specificity of interactions between mDia isoforms and Rho proteins. J Biol Chem. 2008 Dec 12;283(50):35236-46. Epub 2008 Sep 30. PMID:18829452 doi:10.1074/jbc.M805634200

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3eg5"

@@ Line 1: / Line 1: @@
 ==Crystal structure of MDIA1-TSH GBD-FH3 in complex with CDC42-GMPPNP==
 <StructureSection load='3eg5' size='340' side='right' caption='[[3eg5]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1z2c|1z2c]], [[2bap|2bap]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Cdc42 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Diaph1 ([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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3eg5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3eg5 OCA], [http://pdbe.org/3eg5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3eg5 RCSB], [http://www.ebi.ac.uk/pdbsum/3eg5 PDBsum]</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=3eg5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3eg5 OCA], [http://pdbe.org/3eg5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3eg5 RCSB], [http://www.ebi.ac.uk/pdbsum/3eg5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3eg5 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 14: / Line 15: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/eg/3eg5_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/eg/3eg5_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 42: / Line 43: @@
 [[Category: Wittinghofer, A]]
 [[Category: Actin-binding]]
+[[Category: Alternative splicing]]
 [[Category: Armadillo repeat]]
 [[Category: Cell membrane]]
 [[Category: Cell projection]]
+[[Category: Coiled coil]]
+[[Category: Cytoplasm]]
 [[Category: Cytoskeleton]]
 [[Category: Diaphanous]]
@@ Line 60: / Line 64: @@
 [[Category: Rho protein]]
 [[Category: Signaling protein]]
+[[Category: Ubl conjugation]]

3eg5

From Proteopedia

Revision as of 22:02, 2 December 2018

Crystal structure of MDIA1-TSH GBD-FH3 in complex with CDC42-GMPPNP

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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