2oan: Difference between revisions

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-[[Image:2oan.jpg|left|200px]]<br /><applet load="2oan" size="350" color="white" frame="true" align="right" spinBox="true"
-caption="2oan, resolution 2.606&Aring;" />
-'''Structure of oxidized beta-actin'''<br />
-==Overview==
+==Structure of oxidized beta-actin==
-An essential consequence of growth factor-mediated signal transduction is, the generation of intracellular H(2)O(2). It operates as a second, messenger in the control of actin microfilament dynamics, causing rapid, and dramatic changes in the morphology and motile activity of stimulated, cells. Little is understood about the molecular mechanisms causing these, changes in the actin system. Here, it is shown that H(2)O(2) acts directly, upon several levels of this system, and some of the mechanistic effects, are detailed. We describe the impact of oxidation on the polymerizability, of non-muscle beta/gamma-actin and compare with that of muscle, alpha-actin. Oxidation of beta/gamma-actin can cause a complete loss of, polymerizability, crucially, reversible by the thioredoxin system., Further, oxidation of the actin impedes its interaction with profilin and, causes depolymerization of filamentous actin. The effects of oxidation are, critically dependent on the nucleotide state and the concentration of, Ca(2+). We have determined the crystal structure of oxidized beta-actin to, a resolution of 2.6 A. The arrangement in the crystal implies an, antiparallel homodimer connected by an intermolecular disulfide bond, involving cysteine 374. Our data indicate that this dimer forms under, non-polymerizing and oxidizing conditions. We identify oxidation of, cysteine 272 in the crystallized actin dimer, likely to a cysteine, sulfinic acid. In beta/gamma-actin, this is the cysteine residue most, reactive towards H(2)O(2) in solution, and we suggest plausible structural, determinants for its reactivity. No other oxidative modification was, obvious in the structure, highlighting the specificity of the oxidation by, H(2)O(2). Possible consequences of the observed effects in a cellular, context and their potential relevance are discussed.
+<StructureSection load='2oan' size='340' side='right'caption='[[2oan]], [[Resolution|resolution]] 2.61&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2oan]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OAN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2OAN FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.606&#8491;</td></tr>
+<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=CSD:3-SULFINOALANINE'>CSD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=2oan FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2oan OCA], [https://pdbe.org/2oan PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2oan RCSB], [https://www.ebi.ac.uk/pdbsum/2oan PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2oan ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/ACTB_BOVIN ACTB_BOVIN] 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 ==
+An essential consequence of growth factor-mediated signal transduction is the generation of intracellular H(2)O(2). It operates as a second messenger in the control of actin microfilament dynamics, causing rapid and dramatic changes in the morphology and motile activity of stimulated cells. Little is understood about the molecular mechanisms causing these changes in the actin system. Here, it is shown that H(2)O(2) acts directly upon several levels of this system, and some of the mechanistic effects are detailed. We describe the impact of oxidation on the polymerizability of non-muscle beta/gamma-actin and compare with that of muscle alpha-actin. Oxidation of beta/gamma-actin can cause a complete loss of polymerizability, crucially, reversible by the thioredoxin system. Further, oxidation of the actin impedes its interaction with profilin and causes depolymerization of filamentous actin. The effects of oxidation are critically dependent on the nucleotide state and the concentration of Ca(2+). We have determined the crystal structure of oxidized beta-actin to a resolution of 2.6 A. The arrangement in the crystal implies an antiparallel homodimer connected by an intermolecular disulfide bond involving cysteine 374. Our data indicate that this dimer forms under non-polymerizing and oxidizing conditions. We identify oxidation of cysteine 272 in the crystallized actin dimer, likely to a cysteine sulfinic acid. In beta/gamma-actin, this is the cysteine residue most reactive towards H(2)O(2) in solution, and we suggest plausible structural determinants for its reactivity. No other oxidative modification was obvious in the structure, highlighting the specificity of the oxidation by H(2)O(2). Possible consequences of the observed effects in a cellular context and their potential relevance are discussed.
-==About this Structure==
+Molecular and structural basis for redox regulation of beta-actin.,Lassing I, Schmitzberger F, Bjornstedt M, Holmgren A, Nordlund P, Schutt CE, Lindberg U J Mol Biol. 2007 Jul 6;370(2):331-48. Epub 2007 May 4. PMID:17521670<ref>PMID:17521670</ref>
-OAN is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with <scene name='pdbligand=CA:'>CA</scene>, <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=OC4:'>OC4</scene> and <scene name='pdbligand=ATP:'>ATP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OAN OCA].
-==Reference==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-Molecular and Structural Basis for Redox Regulation of beta-Actin., Lassing I, Schmitzberger F, Bjornstedt M, Holmgren A, Nordlund P, Schutt CE, Lindberg U, J Mol Biol. 2007 Jul 6;370(2):331-48. Epub 2007 May 4. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17521670 17521670]
+</div>
+<div class="pdbe-citations 2oan" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Actin 3D structures|Actin 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Bos taurus]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Lassing, I.]]
+[[Category: Lassing I]]
-[[Category: Lindberg, U.]]
+[[Category: Lindberg U]]
-[[Category: Nordlund, P.]]
+[[Category: Nordlund P]]
-[[Category: Schmitzberger, F.]]
+[[Category: Schmitzberger F]]
-[[Category: ATP]]
-[[Category: CA]]
-[[Category: OC4]]
-[[Category: SO4]]
-[[Category: cysteine covalently modified by oxidation]]
-[[Category: disulfide]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 14:53:21 2008''