2n8z: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Apo form of Calmodulin-Like Domain of Human Non-Muscle alpha-actinin 1== | |||
<StructureSection load='2n8z' size='340' side='right' caption='[[2n8z]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2n8z]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2N8Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2N8Z FirstGlance]. <br> | |||
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2n8y|2n8y]]</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2n8z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n8z OCA], [http://pdbe.org/2n8z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2n8z RCSB], [http://www.ebi.ac.uk/pdbsum/2n8z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2n8z ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://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> | |||
</div> | |||
<div class="pdbe-citations 2n8z" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Backman, L]] | [[Category: Backman, L]] | ||
[[Category: Djinovic-Carugo, K]] | [[Category: Djinovic-Carugo, K]] | ||
[[Category: | [[Category: Hartl, M]] | ||
[[Category: Ilc, G]] | [[Category: Ilc, G]] | ||
[[Category: Lenarcic, B]] | |||
[[Category: Pavsic, M]] | |||
[[Category: Plavec, J]] | [[Category: Plavec, J]] | ||
[[Category: Prebil, S Drmota]] | |||
[[Category: Ribeiro, E de Almeida]] | |||
[[Category: Slapsak, U]] | |||
[[Category: Zielinska, K]] | [[Category: Zielinska, K]] | ||
[[Category: | [[Category: Calcium binding protein]] | ||
[[Category: | [[Category: Structural protein]] | ||
Revision as of 13:11, 13 July 2016
Apo form of Calmodulin-Like Domain of Human Non-Muscle alpha-actinin 1Apo form of Calmodulin-Like Domain of Human Non-Muscle alpha-actinin 1
Structural highlights
Function[ACTN1_HUMAN] F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein. Publication Abstract from PubMedThe 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||