3obv

From Proteopedia

(Difference between revisions)

Revision as of 14:49, 24 December 2014

Autoinhibited Formin mDia1 Structure

Structural highlights

3obv is a 8 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:
Related:	1v9d, 2bnx
Gene:	Diaph1, Diap1 (Mus musculus)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[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]

Publication Abstract from PubMed

BACKGROUND: Formin proteins utilize a conserved formin homology 2 (FH2) domain to nucleate new actin filaments. In mammalian diaphanous-related formins (DRFs) the FH2 domain is inhibited through an unknown mechanism by intramolecular binding of the diaphanous autoinhibitory domain (DAD) and the diaphanous inhibitory domain (DID). METHODOLOGY/PRINCIPAL FINDINGS: Here we report the crystal structure of a complex between DID and FH2-DAD fragments of the mammalian DRF, mDia1 (mammalian diaphanous 1 also called Drf1 or p140mDia). The structure shows a tetrameric configuration (4 FH2 + 4 DID) in which the actin-binding sites on the FH2 domain are sterically occluded. However biochemical data suggest the full-length mDia1 is a dimer in solution (2 FH2 + 2 DID). Based on the crystal structure, we have generated possible dimer models and found that architectures of all of these models are incompatible with binding to actin filament but not to actin monomer. Furthermore, we show that the minimal functional monomeric unit in the FH2 domain, termed the bridge element, can be inhibited by isolated monomeric DID. NMR data on the bridge-DID system revealed that at least one of the two actin-binding sites on the bridge element is accessible to actin monomer in the inhibited state. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that autoinhibition in the native DRF dimer involves steric hindrance with the actin filament. Although the structure of a full-length DRF would be required for clarification of the presented models, our work here provides the first structural insights into the mechanism of the DRF autoinhibition.

Crystal structure of the Formin mDia1 in autoinhibited conformation.,Otomo T, Tomchick DR, Otomo C, Machius M, Rosen MK PLoS One. 2010 Sep 30;5(9). pii: e12896. PMID:20927343^[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
↑ Otomo T, Tomchick DR, Otomo C, Machius M, Rosen MK. Crystal structure of the Formin mDia1 in autoinhibited conformation. PLoS One. 2010 Sep 30;5(9). pii: e12896. PMID:20927343 doi:10.1371/journal.pone.0012896

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[3obv]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OBV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3OBV FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SUC:SUCROSE'>SUC</scene><br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SUC:SUCROSE'>SUC</scene></td></tr>
-<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1v9d|1v9d]], [[2bnx|2bnx]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1v9d|1v9d]], [[2bnx|2bnx]]</td></tr>
-<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Diaph1, Diap1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Diaph1, Diap1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])</td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3obv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3obv OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3obv RCSB], [http://www.ebi.ac.uk/pdbsum/3obv 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=3obv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3obv OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3obv RCSB], [http://www.ebi.ac.uk/pdbsum/3obv PDBsum]</span></td></tr>
-<table>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/DIAP1_MOUSE 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).<ref>PMID:9214622</ref> <ref>PMID:10678165</ref> <ref>PMID:15044801</ref> <ref>PMID:18572016</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 14: / Line 16: @@
 Crystal structure of the Formin mDia1 in autoinhibited conformation.,Otomo T, Tomchick DR, Otomo C, Machius M, Rosen MK PLoS One. 2010 Sep 30;5(9). pii: e12896. PMID:20927343<ref>PMID:20927343</ref>
-From MEDLINEÂ®/PubMedÂ®, a database of the U.S. National Library of Medicine.<br>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
 == References ==
@@ Line 21: / Line 23: @@
 </StructureSection>
 [[Category: Mus musculus]]
-[[Category: Otomo, T.]]
+[[Category: Otomo, T]]
-[[Category: Rosen, M K.]]
+[[Category: Rosen, M K]]
-[[Category: Tomchick, D R.]]
+[[Category: Tomchick, D R]]
 [[Category: Actin]]
 [[Category: Autoinhibition]]

3obv

From Proteopedia

Revision as of 14:49, 24 December 2014

Autoinhibited Formin mDia1 Structure

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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