7utl: Difference between revisions
New page: '''Unreleased structure''' The entry 7utl is ON HOLD Authors: Rynkiewicz, M.J., Pavadai, E., Lehman, W. Description: ALTERNATIVE MODELING OF TROPOMYOSIN IN HUMAN CARDIAC THIN FILAMENT ... |
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==ALTERNATIVE MODELING OF TROPOMYOSIN IN HUMAN CARDIAC THIN FILAMENT IN THE CALCIUM FREE STATE== | |||
<StructureSection load='7utl' size='340' side='right'caption='[[7utl]], [[Resolution|resolution]] 6.60Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7utl]] is a 34 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UTL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UTL 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=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=7utl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7utl OCA], [https://pdbe.org/7utl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7utl RCSB], [https://www.ebi.ac.uk/pdbsum/7utl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7utl 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 == | |||
Experimental approaches such as fiber diffraction and cryo-electron microscopy reconstruction have defined regulatory positions of tropomyosin on actin but have not, as yet, succeeded at determining key atomic-level contacts between these proteins or fully substantiated the dynamics of their interactions at a structural level. To overcome this deficiency, we have previously employed computational approaches to deduce global dynamics of thin filament components by energy landscape determination and molecular dynamics simulations. Still, these approaches remain computationally challenging for any complex and large macromolecular assembly like the thin filament. For example, tropomyosin cable wrapping around actin of thin filaments features both head-to-tail polymeric interactions and local twisting, both of which depart from strict superhelical symmetry. This produces a complex energy surface that is difficult to model and thus to evaluate globally. Therefore, at this stage of our understanding, assessing global molecular dynamics can prove to be inherently impractical. As an alternative, we adopted a "divide and conquer" protocol to investigate actin-tropomyosin interactions at an atomistic level. Here, we first employed unbiased protein-protein docking tools to identify binding specificity of individual tropomyosin pseudorepeat segments over the actin surface. Accordingly, tropomyosin "ligand" segments were rotated and translated over potential "target" binding sites on F-actin where the corresponding interaction energetics of billions of conformational poses were ranked by the programs PIPER and ClusPro. These data were used to assess favorable interactions and then to rebuild models of seamless and continuous tropomyosin cables over the F-actin substrate, which were optimized further by flexible fitting routines and molecular dynamics. The models generated azimuthally distinct regulatory positions for tropomyosin cables along thin filaments on actin dominated by stereo-specific head-to-tail overlap linkage. The outcomes are in good agreement with current cryo-electron microscopy topology and consistent with long-thought residue-to-residue interactions between actin and tropomyosin. | |||
Protein-Protein Docking Reveals Dynamic Interactions of Tropomyosin on Actin Filaments.,Pavadai E, Lehman W, Rynkiewicz MJ Biophys J. 2020 Jul 7;119(1):75-86. doi: 10.1016/j.bpj.2020.05.017. Epub 2020 May, 22. PMID:32521240<ref>PMID:32521240</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Lehman | <div class="pdbe-citations 7utl" style="background-color:#fffaf0;"></div> | ||
[[Category: Pavadai | == References == | ||
[[Category: Rynkiewicz | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Oryctolagus cuniculus]] | |||
[[Category: Lehman W]] | |||
[[Category: Pavadai E]] | |||
[[Category: Rynkiewicz MJ]] | |||
Latest revision as of 10:39, 21 September 2022
ALTERNATIVE MODELING OF TROPOMYOSIN IN HUMAN CARDIAC THIN FILAMENT IN THE CALCIUM FREE STATEALTERNATIVE MODELING OF TROPOMYOSIN IN HUMAN CARDIAC THIN FILAMENT IN THE CALCIUM FREE STATE
Structural highlights
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 PubMedExperimental approaches such as fiber diffraction and cryo-electron microscopy reconstruction have defined regulatory positions of tropomyosin on actin but have not, as yet, succeeded at determining key atomic-level contacts between these proteins or fully substantiated the dynamics of their interactions at a structural level. To overcome this deficiency, we have previously employed computational approaches to deduce global dynamics of thin filament components by energy landscape determination and molecular dynamics simulations. Still, these approaches remain computationally challenging for any complex and large macromolecular assembly like the thin filament. For example, tropomyosin cable wrapping around actin of thin filaments features both head-to-tail polymeric interactions and local twisting, both of which depart from strict superhelical symmetry. This produces a complex energy surface that is difficult to model and thus to evaluate globally. Therefore, at this stage of our understanding, assessing global molecular dynamics can prove to be inherently impractical. As an alternative, we adopted a "divide and conquer" protocol to investigate actin-tropomyosin interactions at an atomistic level. Here, we first employed unbiased protein-protein docking tools to identify binding specificity of individual tropomyosin pseudorepeat segments over the actin surface. Accordingly, tropomyosin "ligand" segments were rotated and translated over potential "target" binding sites on F-actin where the corresponding interaction energetics of billions of conformational poses were ranked by the programs PIPER and ClusPro. These data were used to assess favorable interactions and then to rebuild models of seamless and continuous tropomyosin cables over the F-actin substrate, which were optimized further by flexible fitting routines and molecular dynamics. The models generated azimuthally distinct regulatory positions for tropomyosin cables along thin filaments on actin dominated by stereo-specific head-to-tail overlap linkage. The outcomes are in good agreement with current cryo-electron microscopy topology and consistent with long-thought residue-to-residue interactions between actin and tropomyosin. Protein-Protein Docking Reveals Dynamic Interactions of Tropomyosin on Actin Filaments.,Pavadai E, Lehman W, Rynkiewicz MJ Biophys J. 2020 Jul 7;119(1):75-86. doi: 10.1016/j.bpj.2020.05.017. Epub 2020 May, 22. PMID:32521240[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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