2n8y: Difference between revisions
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The | ==Holo form of Calmodulin-Like Domain of Human Non-Muscle alpha-actinin 1== | ||
<StructureSection load='2n8y' size='340' side='right'caption='[[2n8y]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2n8y]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2N8Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2N8Y FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</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=2n8y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n8y OCA], [https://pdbe.org/2n8y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2n8y RCSB], [https://www.ebi.ac.uk/pdbsum/2n8y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2n8y ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/ACTN1_HUMAN ACTN1_HUMAN] F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The activity of several cytosolic proteins critically depends on the concentration of calcium ions. One important intracellular calcium-sensing protein is alpha-actinin-1, the major actin crosslinking protein in focal adhesions and stress fibers. The actin crosslinking activity of alpha-actinin-1 has been proposed to be negatively regulated by calcium, but the underlying molecular mechanisms are poorly understood. To address this, we determined the first high-resolution NMR structure of its functional calmodulin-like domain (CaMD) in calcium-bound and calcium-free form. These structures reveal that in the absence of calcium, CaMD displays a conformationally flexible ensemble that undergoes a structural change upon calcium binding, leading to limited rotation of the N- and C-terminal lobes around the connecting linker and consequent stabilization of the calcium-loaded structure. Mutagenesis experiments, coupled with mass-spectrometry and isothermal calorimetry data designed to validate the calcium binding stoichiometry and binding site, showed that human non-muscle alpha-actinin-1 binds a single calcium ion within the N-terminal lobe. Finally, based on our structural data and analogy with other alpha-actinins, we provide a structural model of regulation of the actin crosslinking activity of alpha-actinin-1 where calcium induced structural stabilisation causes fastening of the juxtaposed actin binding domain, leading to impaired capacity to crosslink actin. | |||
Structure and calcium-binding studies of calmodulin-like domain of human non-muscle alpha-actinin-1.,Drmota Prebil S, Slapsak U, Pavsic M, Ilc G, Puz V, de Almeida Ribeiro E, Anrather D, Hartl M, Backman L, Plavec J, Lenarcic B, Djinovic-Carugo K Sci Rep. 2016 Jun 7;6:27383. doi: 10.1038/srep27383. PMID:27272015<ref>PMID:27272015</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Backman | <div class="pdbe-citations 2n8y" style="background-color:#fffaf0;"></div> | ||
[[Category: Djinovic-Carugo | |||
[[Category: | ==See Also== | ||
[[Category: | *[[Actinin 3D structures|Actinin 3D structures]] | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: De Almeida Ribeiro | [[Category: Backman L]] | ||
[[Category: Djinovic-Carugo K]] | |||
[[Category: Drmota Prebil S]] | |||
[[Category: Hartl M]] | |||
[[Category: Ilc G]] | |||
[[Category: Lenarcic B]] | |||
[[Category: Pavsic M]] | |||
[[Category: Plavec J]] | |||
[[Category: Slapsak U]] | |||
[[Category: Zielinska K]] | |||
[[Category: De Almeida Ribeiro E]] | |||