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| | ==The NMR Structure of the Cdc42-interacting region of TOCA1== | | ==The NMR Structure of the Cdc42-interacting region of TOCA1== |
| - | <StructureSection load='5frg' size='340' side='right'caption='[[5frg]], [[NMR_Ensembles_of_Models | 35 NMR models]]' scene=''> | + | <StructureSection load='5frg' size='340' side='right'caption='[[5frg]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5frg]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Silurana_(xenopus)_tropicalis Silurana (xenopus) tropicalis]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FRG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5FRG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5frg]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Xenopus_tropicalis Xenopus tropicalis]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FRG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5FRG 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=5frg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5frg OCA], [http://pdbe.org/5frg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5frg RCSB], [http://www.ebi.ac.uk/pdbsum/5frg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5frg ProSAT]</span></td></tr> | + | </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=5frg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5frg OCA], [https://pdbe.org/5frg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5frg RCSB], [https://www.ebi.ac.uk/pdbsum/5frg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5frg ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/FBP1L_XENTR FBP1L_XENTR]] Required to coordinate membrane tubulation with reorganization of the actin cytoskeleton during endocytosis. Promotes cdc42-induced actin polymerization by activating the wasl-waspip complex, the predominant form of wasl/n-wasp in cells. Essential for autophagy of intracellular bacterial pathogens (By similarity). | + | [https://www.uniprot.org/uniprot/FBP1L_XENTR FBP1L_XENTR] Required to coordinate membrane tubulation with reorganization of the actin cytoskeleton during endocytosis. Promotes cdc42-induced actin polymerization by activating the wasl-waspip complex, the predominant form of wasl/n-wasp in cells. Essential for autophagy of intracellular bacterial pathogens (By similarity). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Mott, H R]] | + | [[Category: Xenopus tropicalis]] |
| - | [[Category: Nietlispach, D]] | + | [[Category: Mott HR]] |
| - | [[Category: Owen, D]] | + | [[Category: Nietlispach D]] |
| - | [[Category: Watson, J R]] | + | [[Category: Owen D]] |
| - | [[Category: Cdc42]] | + | [[Category: Watson JR]] |
| - | [[Category: Cytoskeleton]]
| + | |
| - | [[Category: Endocytosis]]
| + | |
| - | [[Category: Formin-binding protein like-1]]
| + | |
| - | [[Category: Hr1]]
| + | |
| - | [[Category: Lipid-binding]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Plasma membrane]]
| + | |
| - | [[Category: Protein binding]]
| + | |
| - | [[Category: Rem]]
| + | |
| - | [[Category: Rho family]]
| + | |
| - | [[Category: Small g protein]]
| + | |
| Structural highlights
Function
FBP1L_XENTR Required to coordinate membrane tubulation with reorganization of the actin cytoskeleton during endocytosis. Promotes cdc42-induced actin polymerization by activating the wasl-waspip complex, the predominant form of wasl/n-wasp in cells. Essential for autophagy of intracellular bacterial pathogens (By similarity).
Publication Abstract from PubMed
Transducer of Cdc42-dependent actin assembly protein 1 (TOCA1) is an effector of the Rho family small G protein Cdc42. It contains a membrane-deforming F-BAR domain as well as an SH3 domain and a G protein-binding HR1 (homology region 1) domain. TOCA1 binding to Cdc42 leads to actin rearrangements, which are thought to be involved in processes such as endocytosis, filopodia formation and cell migration. We have solved the structure of the HR1 domain of TOCA1, providing the first structural data for this protein. We have found that the TOCA1 HR1, like the closely related CIP4 HR1, has interesting structural features that are not observed in other HR1 domains. We have also investigated the binding of the TOCA HR1 domain to Cdc42, and the potential ternary complex between Cdc42 and the G protein binding regions of TOCA1 and a member of the Wiskott-Aldrich syndrome protein family, N-WASP. TOCA1 binds Cdc42 with micromolar affinity, in contrast to the nanomolar affinity of the N-WASP G protein binding region for Cdc42. NMR experiments show that the Cdc42 binding domain from N-WASP is able to displace TOCA1 HR1 from Cdc42, while the N-WASP domain but not the TOCA1 HR1 domain inhibits actin polymerisation. This suggests that TOCA1 binding to Cdc42 is an early step in the Cdc42-dependent pathways that govern actin dynamics and the differential binding affinities of the effectors facilitate a handover from TOCA1 to N-WASP, which can then drive recruitment of the actin modifying machinery.
Investigation of the Interaction Between Cdc42 and its Effector TOCA1: Handover of Cdc42 to the Actin Regulator N-WASP is Facilitated by Differential Binding Affinities.,Watson JR, Fox HM, Nietlispach D, Gallop JL, Owen D, Mott HR J Biol Chem. 2016 Apr 22. pii: jbc.M116.724294. PMID:27129201[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Watson JR, Fox HM, Nietlispach D, Gallop JL, Owen D, Mott HR. Investigation of the Interaction Between Cdc42 and its Effector TOCA1: Handover of Cdc42 to the Actin Regulator N-WASP is Facilitated by Differential Binding Affinities. J Biol Chem. 2016 Apr 22. pii: jbc.M116.724294. PMID:27129201 doi:http://dx.doi.org/10.1074/jbc.M116.724294
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