6duy

From Proteopedia

(Difference between revisions)

Revision as of 08:24, 19 December 2018

Crystal structure of the alpha-N-catenin actin-binding domain H1 mutant

Structural highlights

6duy is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[CTNA2_MOUSE] May function as a linker between cadherin adhesion receptors and the cytoskeleton to regulate cell-cell adhesion and differentiation in the nervous system. Regulates morphological plasticity of synapses and cerebellar and hippocampal lamination during development. Functions in the control of startle modulation.^[1] ^[2] ^[3]

Publication Abstract from PubMed

alpha-catenin is a key mechanosensor that forms force-dependent interactions with F-actin, thereby coupling the cadherin-catenin complex to the actin cytoskeleton at adherens junctions (AJs). However, the molecular mechanisms by which alpha-catenin engages F-actin under tension remained elusive. Here we show that the alpha1-helix of the alpha-catenin actin-binding domain (alphacat-ABD) is a mechanosensing motif that regulates tension-dependent F-actin binding and bundling. alphacat-ABD containing an alpha1-helix-unfolding mutation (H1) shows enhanced binding to F-actin in vitro. Although full-length alpha-catenin-H1 can generate epithelial monolayers that resist mechanical disruption, it fails to support normal AJ regulation in vivo. Structural and simulation analyses suggest that alpha1-helix allosterically controls the actin-binding residue V796 dynamics. Crystal structures of alphacat-ABD-H1 homodimer suggest that alpha-catenin can facilitate actin bundling while it remains bound to E-cadherin. We propose that force-dependent allosteric regulation of alphacat-ABD promotes dynamic interactions with F-actin involved in actin bundling, cadherin clustering, and AJ remodeling during tissue morphogenesis.

Force-dependent allostery of the alpha-catenin actin-binding domain controls adherens junction dynamics and functions.,Ishiyama N, Sarpal R, Wood MN, Barrick SK, Nishikawa T, Hayashi H, Kobb AB, Flozak AS, Yemelyanov A, Fernandez-Gonzalez R, Yonemura S, Leckband DE, Gottardi CJ, Tepass U, Ikura M Nat Commun. 2018 Nov 30;9(1):5121. doi: 10.1038/s41467-018-07481-7. PMID:30504777^[4]

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

References

↑ Park C, Falls W, Finger JH, Longo-Guess CM, Ackerman SL. Deletion in Catna2, encoding alpha N-catenin, causes cerebellar and hippocampal lamination defects and impaired startle modulation. Nat Genet. 2002 Jul;31(3):279-84. Epub 2002 Jun 24. PMID:12089526 doi:10.1038/ng908
↑ Togashi H, Abe K, Mizoguchi A, Takaoka K, Chisaka O, Takeichi M. Cadherin regulates dendritic spine morphogenesis. Neuron. 2002 Jul 3;35(1):77-89. PMID:12123610
↑ Abe K, Chisaka O, Van Roy F, Takeichi M. Stability of dendritic spines and synaptic contacts is controlled by alpha N-catenin. Nat Neurosci. 2004 Apr;7(4):357-63. Epub 2004 Mar 21. PMID:15034585 doi:10.1038/nn1212
↑ Ishiyama N, Sarpal R, Wood MN, Barrick SK, Nishikawa T, Hayashi H, Kobb AB, Flozak AS, Yemelyanov A, Fernandez-Gonzalez R, Yonemura S, Leckband DE, Gottardi CJ, Tepass U, Ikura M. Force-dependent allostery of the alpha-catenin actin-binding domain controls adherens junction dynamics and functions. Nat Commun. 2018 Nov 30;9(1):5121. doi: 10.1038/s41467-018-07481-7. PMID:30504777 doi:http://dx.doi.org/10.1038/s41467-018-07481-7

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/6duy"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6duy is ON HOLD  until Paper Publication
+==Crystal structure of the alpha-N-catenin actin-binding domain H1 mutant==
+<StructureSection load='6duy' size='340' side='right' caption='[[6duy]], [[Resolution|resolution]] 2.81&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6duy]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DUY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DUY FirstGlance]. <br>
+</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=6duy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6duy OCA], [http://pdbe.org/6duy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6duy RCSB], [http://www.ebi.ac.uk/pdbsum/6duy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6duy ProSAT]</span></td></tr>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/CTNA2_MOUSE CTNA2_MOUSE]] May function as a linker between cadherin adhesion receptors and the cytoskeleton to regulate cell-cell adhesion and differentiation in the nervous system. Regulates morphological plasticity of synapses and cerebellar and hippocampal lamination during development. Functions in the control of startle modulation.<ref>PMID:12089526</ref> <ref>PMID:12123610</ref> <ref>PMID:15034585</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+alpha-catenin is a key mechanosensor that forms force-dependent interactions with F-actin, thereby coupling the cadherin-catenin complex to the actin cytoskeleton at adherens junctions (AJs). However, the molecular mechanisms by which alpha-catenin engages F-actin under tension remained elusive. Here we show that the alpha1-helix of the alpha-catenin actin-binding domain (alphacat-ABD) is a mechanosensing motif that regulates tension-dependent F-actin binding and bundling. alphacat-ABD containing an alpha1-helix-unfolding mutation (H1) shows enhanced binding to F-actin in vitro. Although full-length alpha-catenin-H1 can generate epithelial monolayers that resist mechanical disruption, it fails to support normal AJ regulation in vivo. Structural and simulation analyses suggest that alpha1-helix allosterically controls the actin-binding residue V796 dynamics. Crystal structures of alphacat-ABD-H1 homodimer suggest that alpha-catenin can facilitate actin bundling while it remains bound to E-cadherin. We propose that force-dependent allosteric regulation of alphacat-ABD promotes dynamic interactions with F-actin involved in actin bundling, cadherin clustering, and AJ remodeling during tissue morphogenesis.
-Authors: Ishiyama, N., Ikura, M.
+Force-dependent allostery of the alpha-catenin actin-binding domain controls adherens junction dynamics and functions.,Ishiyama N, Sarpal R, Wood MN, Barrick SK, Nishikawa T, Hayashi H, Kobb AB, Flozak AS, Yemelyanov A, Fernandez-Gonzalez R, Yonemura S, Leckband DE, Gottardi CJ, Tepass U, Ikura M Nat Commun. 2018 Nov 30;9(1):5121. doi: 10.1038/s41467-018-07481-7. PMID:30504777<ref>PMID:30504777</ref>
-Description: Crystal structure of the alpha-N-catenin actin-binding domain H1 mutant
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 6duy" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Ikura, M]]
 [[Category: Ishiyama, N]]
+[[Category: Cell adhesion]]
+[[Category: F-actin-binding]]
+[[Category: Five-helix bundle]]
+[[Category: Mechanosensor]]

6duy

From Proteopedia

Revision as of 08:24, 19 December 2018

Crystal structure of the alpha-N-catenin actin-binding domain H1 mutant

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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