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| | ==Crystal Structure Analysis of Dysferlin C2A variant 1 (C2Av1)== | | ==Crystal Structure Analysis of Dysferlin C2A variant 1 (C2Av1)== |
| - | <StructureSection load='4iqh' size='340' side='right' caption='[[4iqh]], [[Resolution|resolution]] 1.76Å' scene=''> | + | <StructureSection load='4iqh' size='340' side='right'caption='[[4iqh]], [[Resolution|resolution]] 1.76Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4iqh]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IQH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IQH FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4iqh]] is a 3 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=4IQH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IQH FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3l9b|3l9b]], [[2dmh|2dmh]], [[4ihb|4ihb]]</td></tr> | + | </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=4iqh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iqh OCA], [https://pdbe.org/4iqh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4iqh RCSB], [https://www.ebi.ac.uk/pdbsum/4iqh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4iqh ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DYSF, Dysferlin, FER1L1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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| - | <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=4iqh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iqh OCA], [http://pdbe.org/4iqh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4iqh RCSB], [http://www.ebi.ac.uk/pdbsum/4iqh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4iqh ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://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. | + | [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 == | | == Function == |
| - | [[http://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). | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Fuson, K L]] | + | [[Category: Large Structures]] |
| - | [[Category: Sutton, R B]] | + | [[Category: Fuson KL]] |
| - | [[Category: Acidic phospholipid binding]] | + | [[Category: Sutton RB]] |
| - | [[Category: C2 domain]]
| + | |
| - | [[Category: Membrane protein]]
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| - | [[Category: Membrane repair]]
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| - | [[Category: Peripheral membrane protein]]
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| Structural highlights
Disease
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
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).
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Fuson K, Rice A, Mahling R, Snow A, Nayak K, Shanbhogue P, Meyer AG, Redpath GM, Hinderliter A, Cooper ST, Sutton RB. Alternate Splicing of Dysferlin C2A Confers Ca-Dependent and Ca-Independent Binding for Membrane Repair. Structure. 2013 Nov 13. pii: S0969-2126(13)00392-4. doi:, 10.1016/j.str.2013.10.001. PMID:24239457 doi:http://dx.doi.org/10.1016/j.str.2013.10.001
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