8a2r: Difference between revisions
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The | ==Cryo-EM structure of F-actin in the Mg2+-ADP-BeF3- nucleotide state.== | ||
<StructureSection load='8a2r' size='340' side='right'caption='[[8a2r]], [[Resolution|resolution]] 2.17Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8a2r]] is a 5 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=8A2R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8A2R FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=BEF:BERYLLIUM+TRIFLUORIDE+ION'>BEF</scene>, <scene name='pdbligand=HIC:4-METHYL-HISTIDINE'>HIC</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=8a2r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8a2r OCA], [https://pdbe.org/8a2r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8a2r RCSB], [https://www.ebi.ac.uk/pdbsum/8a2r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8a2r 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 == | |||
The dynamic turnover of actin filaments (F-actin) controls cellular motility in eukaryotes and is coupled to changes in the F-actin nucleotide state<sup>1-3</sup>. It remains unclear how F-actin hydrolyses ATP and subsequently undergoes subtle conformational rearrangements that ultimately lead to filament depolymerization by actin-binding proteins. Here we present cryo-electron microscopy structures of F-actin in all nucleotide states, polymerized in the presence of Mg<sup>2+</sup> or Ca<sup>2+</sup> at approximately 2.2 A resolution. The structures show that actin polymerization induces the relocation of water molecules in the nucleotide-binding pocket, activating one of them for the nucleophilic attack of ATP. Unexpectedly, the back door for the subsequent release of inorganic phosphate (P<sub>i</sub>) is closed in all structures, indicating that P<sub>i</sub> release occurs transiently. The small changes in the nucleotide-binding pocket after ATP hydrolysis and P<sub>i</sub> release are sensed by a key amino acid, amplified and transmitted to the filament periphery. Furthermore, differences in the positions of water molecules in the nucleotide-binding pocket explain why Ca<sup>2+</sup>-actin shows slower polymerization rates than Mg<sup>2+</sup>-actin. Our work elucidates the solvent-driven rearrangements that govern actin filament assembly and aging and lays the foundation for the rational design of drugs and small molecules for imaging and therapeutic applications. | |||
Structural basis of actin filament assembly and aging.,Oosterheert W, Klink BU, Belyy A, Pospich S, Raunser S Nature. 2022 Nov;611(7935):374-379. doi: 10.1038/s41586-022-05241-8. Epub 2022, Oct 26. PMID:36289337<ref>PMID:36289337</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 8a2r" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: Klink | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: Raunser | </StructureSection> | ||
[[Category: Large Structures]] | |||
[[Category: Oryctolagus cuniculus]] | |||
[[Category: Belyy A]] | |||
[[Category: Klink BU]] | |||
[[Category: Oosterheert W]] | |||
[[Category: Pospich S]] | |||
[[Category: Raunser S]] | |||
Latest revision as of 23:29, 16 November 2022
Cryo-EM structure of F-actin in the Mg2+-ADP-BeF3- nucleotide state.Cryo-EM structure of F-actin in the Mg2+-ADP-BeF3- nucleotide state.
Structural highlights
FunctionACTS_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 PubMedThe dynamic turnover of actin filaments (F-actin) controls cellular motility in eukaryotes and is coupled to changes in the F-actin nucleotide state<sup>1-3</sup>. It remains unclear how F-actin hydrolyses ATP and subsequently undergoes subtle conformational rearrangements that ultimately lead to filament depolymerization by actin-binding proteins. Here we present cryo-electron microscopy structures of F-actin in all nucleotide states, polymerized in the presence of Mg<sup>2+</sup> or Ca<sup>2+</sup> at approximately 2.2 A resolution. The structures show that actin polymerization induces the relocation of water molecules in the nucleotide-binding pocket, activating one of them for the nucleophilic attack of ATP. Unexpectedly, the back door for the subsequent release of inorganic phosphate (P<sub>i</sub>) is closed in all structures, indicating that P<sub>i</sub> release occurs transiently. The small changes in the nucleotide-binding pocket after ATP hydrolysis and P<sub>i</sub> release are sensed by a key amino acid, amplified and transmitted to the filament periphery. Furthermore, differences in the positions of water molecules in the nucleotide-binding pocket explain why Ca<sup>2+</sup>-actin shows slower polymerization rates than Mg<sup>2+</sup>-actin. Our work elucidates the solvent-driven rearrangements that govern actin filament assembly and aging and lays the foundation for the rational design of drugs and small molecules for imaging and therapeutic applications. Structural basis of actin filament assembly and aging.,Oosterheert W, Klink BU, Belyy A, Pospich S, Raunser S Nature. 2022 Nov;611(7935):374-379. doi: 10.1038/s41586-022-05241-8. Epub 2022, Oct 26. PMID:36289337[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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