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[[Image:2q0r.gif|left|200px]]


{{Structure
==Structure of Pectenotoxin-2 Bound to Actin==
|PDB= 2q0r |SIZE=350|CAPTION= <scene name='initialview01'>2q0r</scene>, resolution 1.700&Aring;
<StructureSection load='2q0r' size='340' side='right'caption='[[2q0r]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
|SITE=  
== Structural highlights ==
|LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=ATP:ADENOSINE-5'-TRIPHOSPHATE'>ATP</scene> and <scene name='pdbligand=PXT:PECTENOTOXIN-2'>PXT</scene>
<table><tr><td colspan='2'>[[2q0r]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q0R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Q0R FirstGlance]. <br>
|ACTIVITY=  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</td></tr>
|GENE=  
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=PXT:PECTENOTOXIN-2'>PXT</scene></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=2q0r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q0r OCA], [https://pdbe.org/2q0r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2q0r RCSB], [https://www.ebi.ac.uk/pdbsum/2q0r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2q0r ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ACTS_RABIT ACTS_RABIT] Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
(PTXs) are polyether macrolides found in certain dinoflagellates, sponges and shellfish, and have been associated with diarrhetic shellfish poisoning. In addition to their in vivo toxicity, some PTXs are potently cytotoxic in human cancer cell lines. Recent studies have demonstrated that disruption of the actin cytoskeleton may be a key function of these compounds, although no clarification of their mechanism of action at a molecular level was available. We have obtained an X-ray crystal structure of PTX-2 bound to actin, which, in combination with analyses of the effect of PTX-2 on purified actin filament dynamics, provides a molecular explanation for its effects on actin. PTX-2 formed a 1:1 complex with actin and engaged a novel site between subdomains 1 and 3. Based on models of the actin filament, PTX binding would disrupt key lateral contacts between the PTX-bound actin monomer and the lower lateral actin monomer within the filament, thereby capping the barbed-end. The location of this binding position within the interior of the filament indicates that it may not be accessible once polymerization has occurred, a hypothesis supported by our observation that PTX-2 caused filament capping without inducing filament severing. This mode of action is unique, as other actin filament destabilizing toxins appear to exclusively disrupt longitudinal monomer contacts, allowing many of them to sever filaments in addition to capping them. Examination of the PTX-binding site on actin provides a rationalization for the structure-activity relationships observed in vivo and in vitro, and may provide a basis for predicting toxicity of PTX analogues.


'''Structure of Pectenotoxin-2 Bound to Actin'''
A structural basis for regulation of actin polymerization by pectenotoxins.,Allingham JS, Miles CO, Rayment I J Mol Biol. 2007 Aug 24;371(4):959-70. Epub 2007 May 25. PMID:17599353<ref>PMID:17599353</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2q0r" style="background-color:#fffaf0;"></div>


==Overview==
==See Also==
(PTXs) are polyether macrolides found in certain dinoflagellates, sponges and shellfish, and have been associated with diarrhetic shellfish poisoning. In addition to their in vivo toxicity, some PTXs are potently cytotoxic in human cancer cell lines. Recent studies have demonstrated that disruption of the actin cytoskeleton may be a key function of these compounds, although no clarification of their mechanism of action at a molecular level was available. We have obtained an X-ray crystal structure of PTX-2 bound to actin, which, in combination with analyses of the effect of PTX-2 on purified actin filament dynamics, provides a molecular explanation for its effects on actin. PTX-2 formed a 1:1 complex with actin and engaged a novel site between subdomains 1 and 3. Based on models of the actin filament, PTX binding would disrupt key lateral contacts between the PTX-bound actin monomer and the lower lateral actin monomer within the filament, thereby capping the barbed-end. The location of this binding position within the interior of the filament indicates that it may not be accessible once polymerization has occurred, a hypothesis supported by our observation that PTX-2 caused filament capping without inducing filament severing. This mode of action is unique, as other actin filament destabilizing toxins appear to exclusively disrupt longitudinal monomer contacts, allowing many of them to sever filaments in addition to capping them. Examination of the PTX-binding site on actin provides a rationalization for the structure-activity relationships observed in vivo and in vitro, and may provide a basis for predicting toxicity of PTX analogues.
*[[Actin 3D structures|Actin 3D structures]]
 
== References ==
==About this Structure==
<references/>
2Q0R is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q0R OCA].
__TOC__
 
</StructureSection>
==Reference==
[[Category: Large Structures]]
A structural basis for regulation of actin polymerization by pectenotoxins., Allingham JS, Miles CO, Rayment I, J Mol Biol. 2007 Aug 24;371(4):959-70. Epub 2007 May 25. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17599353 17599353]
[[Category: Oryctolagus cuniculus]]
[[Category: Oryctolagus cuniculus]]
[[Category: Single protein]]
[[Category: Allingham JS]]
[[Category: Allingham, J S.]]
[[Category: Miles CO]]
[[Category: Miles, C O.]]
[[Category: Rayment I]]
[[Category: Rayment, I.]]
[[Category: ATP]]
[[Category: CA]]
[[Category: PXT]]
[[Category: actin]]
[[Category: anti-tumor]]
[[Category: cytotoxin]]
[[Category: filament capping]]
[[Category: macrolide]]
[[Category: natural product]]
[[Category: pectenotoxin]]
[[Category: structural protein]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:20:17 2008''

Latest revision as of 14:15, 30 August 2023

Structure of Pectenotoxin-2 Bound to ActinStructure of Pectenotoxin-2 Bound to Actin

Structural highlights

2q0r is a 1 chain structure with sequence from Oryctolagus cuniculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.7Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ACTS_RABIT Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.

Publication Abstract from PubMed

(PTXs) are polyether macrolides found in certain dinoflagellates, sponges and shellfish, and have been associated with diarrhetic shellfish poisoning. In addition to their in vivo toxicity, some PTXs are potently cytotoxic in human cancer cell lines. Recent studies have demonstrated that disruption of the actin cytoskeleton may be a key function of these compounds, although no clarification of their mechanism of action at a molecular level was available. We have obtained an X-ray crystal structure of PTX-2 bound to actin, which, in combination with analyses of the effect of PTX-2 on purified actin filament dynamics, provides a molecular explanation for its effects on actin. PTX-2 formed a 1:1 complex with actin and engaged a novel site between subdomains 1 and 3. Based on models of the actin filament, PTX binding would disrupt key lateral contacts between the PTX-bound actin monomer and the lower lateral actin monomer within the filament, thereby capping the barbed-end. The location of this binding position within the interior of the filament indicates that it may not be accessible once polymerization has occurred, a hypothesis supported by our observation that PTX-2 caused filament capping without inducing filament severing. This mode of action is unique, as other actin filament destabilizing toxins appear to exclusively disrupt longitudinal monomer contacts, allowing many of them to sever filaments in addition to capping them. Examination of the PTX-binding site on actin provides a rationalization for the structure-activity relationships observed in vivo and in vitro, and may provide a basis for predicting toxicity of PTX analogues.

A structural basis for regulation of actin polymerization by pectenotoxins.,Allingham JS, Miles CO, Rayment I J Mol Biol. 2007 Aug 24;371(4):959-70. Epub 2007 May 25. PMID:17599353[1]

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

See Also

References

  1. ↑ Allingham JS, Miles CO, Rayment I. A structural basis for regulation of actin polymerization by pectenotoxins. J Mol Biol. 2007 Aug 24;371(4):959-70. Epub 2007 May 25. PMID:17599353 doi:S0022-2836(07)00703-6

2q0r, resolution 1.70Å

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