4ihb: Difference between revisions
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== | ==X-RAY STRUCTURE OF THE canonical C2A DOMAIN FROM HUMAN DYSFERLIN== | ||
[[http://www.uniprot.org/uniprot/DYSF_HUMAN DYSF_HUMAN | <StructureSection load='4ihb' size='340' side='right'caption='[[4ihb]], [[Resolution|resolution]] 2.04Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4ihb]] is a 6 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=4IHB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IHB 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]] 2.044Å</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>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</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=4ihb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ihb OCA], [https://pdbe.org/4ihb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ihb RCSB], [https://www.ebi.ac.uk/pdbsum/4ihb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ihb ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/DYSF_HUMAN DYSF_HUMAN] Miyoshi myopathy;Distal myopathy with anterior tibial onset;Congenital myopathy, Paradas type;Autosomal recessive limb-girdle muscular dystrophy type 2B. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. | |||
== Function == | |||
[https://www.uniprot.org/uniprot/DYSF_HUMAN DYSF_HUMAN] Key calcium ion sensor involved in the Ca(2+)-triggered synaptic vesicle-plasma membrane fusion. Plays a role in the sarcolemma repair mechanism of both skeletal muscle and cardiomyocytes that permits rapid resealing of membranes disrupted by mechanical stress (By similarity). | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Dysferlin plays a critical role in the Ca2+-dependent repair of microlesions that occur in the muscle sarcolemma. Of the seven C2 domains in dysferlin, only C2A is reported to bind both Ca2+ and phospholipid, thus acting as a key sensor in membrane repair. Dysferlin C2A exists as two isoforms, the "canonical" C2A and C2A variant 1 (C2Av1). Interestingly, these isoforms have markedly different responses to Ca2+ and phospholipid. Structural and thermodynamic analyses are consistent with the canonical C2A domain as a Ca2+-dependent, phospholipid-binding domain, whereas C2Av1 would likely be Ca2+-independent under physiological conditions. Additionally, both isoforms display remarkably low free energies of stability, indicative of a highly flexible structure. The inverted ligand preference and flexibility for both C2A isoforms suggest the capability for both constitutive and Ca2+-regulated effector interactions, an activity that would be essential in its role as a mediator of membrane repair. | |||
Alternate Splicing of Dysferlin C2A Confers Ca-Dependent and Ca-Independent Binding for Membrane Repair.,Fuson K, Rice A, Mahling R, Snow A, Nayak K, Shanbhogue P, Meyer AG, Redpath GM, Hinderliter A, Cooper ST, Sutton RB Structure. 2013 Nov 13. pii: S0969-2126(13)00392-4. doi:, 10.1016/j.str.2013.10.001. PMID:24239457<ref>PMID:24239457</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4ihb" style="background-color:#fffaf0;"></div> | |||
= | == References == | ||
<references/> | |||
[[Category: | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Fuson KL]] | |||
[[Category: Sutton RB]] | |||
Latest revision as of 18:22, 20 September 2023
X-RAY STRUCTURE OF THE canonical C2A DOMAIN FROM HUMAN DYSFERLINX-RAY STRUCTURE OF THE canonical C2A DOMAIN FROM HUMAN DYSFERLIN
Structural highlights
DiseaseDYSF_HUMAN Miyoshi myopathy;Distal myopathy with anterior tibial onset;Congenital myopathy, Paradas type;Autosomal recessive limb-girdle muscular dystrophy type 2B. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. FunctionDYSF_HUMAN Key calcium ion sensor involved in the Ca(2+)-triggered synaptic vesicle-plasma membrane fusion. Plays a role in the sarcolemma repair mechanism of both skeletal muscle and cardiomyocytes that permits rapid resealing of membranes disrupted by mechanical stress (By similarity). Publication Abstract from PubMedDysferlin plays a critical role in the Ca2+-dependent repair of microlesions that occur in the muscle sarcolemma. Of the seven C2 domains in dysferlin, only C2A is reported to bind both Ca2+ and phospholipid, thus acting as a key sensor in membrane repair. Dysferlin C2A exists as two isoforms, the "canonical" C2A and C2A variant 1 (C2Av1). Interestingly, these isoforms have markedly different responses to Ca2+ and phospholipid. Structural and thermodynamic analyses are consistent with the canonical C2A domain as a Ca2+-dependent, phospholipid-binding domain, whereas C2Av1 would likely be Ca2+-independent under physiological conditions. Additionally, both isoforms display remarkably low free energies of stability, indicative of a highly flexible structure. The inverted ligand preference and flexibility for both C2A isoforms suggest the capability for both constitutive and Ca2+-regulated effector interactions, an activity that would be essential in its role as a mediator of membrane repair. Alternate Splicing of Dysferlin C2A Confers Ca-Dependent and Ca-Independent Binding for Membrane Repair.,Fuson K, Rice A, Mahling R, Snow A, Nayak K, Shanbhogue P, Meyer AG, Redpath GM, Hinderliter A, Cooper ST, Sutton RB Structure. 2013 Nov 13. pii: S0969-2126(13)00392-4. doi:, 10.1016/j.str.2013.10.001. PMID:24239457[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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