5a38: Difference between revisions
New page: '''Unreleased structure''' The entry 5a38 is ON HOLD Authors: Haywood, N.J., Wolny, M., Trinh, C.H., Shuping, Y., Edwards, T.A., Peckham, M. Description: Mutations in the Calponin homo... |
No edit summary |
||
| (6 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
==Mutations in the Calponin homology domain of Alpha-Actinin-2 affect Actin binding and incorporation in muscle.== | |||
<StructureSection load='5a38' size='340' side='right'caption='[[5a38]], [[Resolution|resolution]] 1.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5a38]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5A38 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5A38 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]] 1.9Å</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=5a38 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5a38 OCA], [https://pdbe.org/5a38 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5a38 RCSB], [https://www.ebi.ac.uk/pdbsum/5a38 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5a38 ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/ACTN2_HUMAN ACTN2_HUMAN] Defects in ACTN2 are the cause of cardiomyopathy dilated type 1AA (CMD1AA) [MIM:[https://omim.org/entry/612158 612158]. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.<ref>PMID:14567970</ref> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/ACTN2_HUMAN ACTN2_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 == | |||
alpha-actinin 2 (ACTN2) is the only muscle isoform of alpha-actinin expressed in cardiac muscle. Mutations in this protein have been implicated in mild to moderate forms of hypertrophic cardiomyopathy (HCM). We have investigated the effects of two mutations identified from HCM patients; A119T and G111V, on the secondary and tertiary structure of a purified actin binding domain of ACTN2 by circular dichroism and X-ray crystallography, and show small but distinct changes for both mutations. We also find that both mutants have reduced F-actin binding affinity, although the differences are not significant. The full length mEos2 tagged protein expressed in adult cardiomyocytes shows that both mutations additionally affect Z-disc localisation and dynamic behaviour. Overall, these two mutations have small effects on structure, function and behaviour, which may contribute to a mild phenotype for this disease. | |||
Hypertrophic Cardiomyopathy Mutations in the calponin-homology domain of ACTN2 affect actin binding and cardiomyocyte Z-disc incorporation.,Haywood N, Wolny M, Rogers B, Trinh CH, Shuping Y, Edwards TA, Peckham M Biochem J. 2016 Jun 10. pii: BCJ20160421. PMID:27287556<ref>PMID:27287556</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[ | </div> | ||
[[Category: | <div class="pdbe-citations 5a38" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: Edwards | ==See Also== | ||
[[Category: Haywood | *[[Actinin 3D structures|Actinin 3D structures]] | ||
[[Category: | == References == | ||
[[Category: Shuping | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Edwards TA]] | |||
[[Category: Haywood NJ]] | |||
[[Category: Peckham M]] | |||
[[Category: Shuping Y]] | |||
[[Category: Trinh CH]] | |||
[[Category: Wolny M]] | |||
Latest revision as of 14:03, 10 January 2024
Mutations in the Calponin homology domain of Alpha-Actinin-2 affect Actin binding and incorporation in muscle.Mutations in the Calponin homology domain of Alpha-Actinin-2 affect Actin binding and incorporation in muscle.
Structural highlights
DiseaseACTN2_HUMAN Defects in ACTN2 are the cause of cardiomyopathy dilated type 1AA (CMD1AA) [MIM:612158. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.[1] FunctionACTN2_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 PubMedalpha-actinin 2 (ACTN2) is the only muscle isoform of alpha-actinin expressed in cardiac muscle. Mutations in this protein have been implicated in mild to moderate forms of hypertrophic cardiomyopathy (HCM). We have investigated the effects of two mutations identified from HCM patients; A119T and G111V, on the secondary and tertiary structure of a purified actin binding domain of ACTN2 by circular dichroism and X-ray crystallography, and show small but distinct changes for both mutations. We also find that both mutants have reduced F-actin binding affinity, although the differences are not significant. The full length mEos2 tagged protein expressed in adult cardiomyocytes shows that both mutations additionally affect Z-disc localisation and dynamic behaviour. Overall, these two mutations have small effects on structure, function and behaviour, which may contribute to a mild phenotype for this disease. Hypertrophic Cardiomyopathy Mutations in the calponin-homology domain of ACTN2 affect actin binding and cardiomyocyte Z-disc incorporation.,Haywood N, Wolny M, Rogers B, Trinh CH, Shuping Y, Edwards TA, Peckham M Biochem J. 2016 Jun 10. pii: BCJ20160421. PMID:27287556[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||