4IHB: X-RAY STRUCTURE OF THE canonical C2A DOMAIN FROM HUMAN DYSFERLIN

Citation:
Abstract
Dysferlin plays a critical role in the Ca(2)(+)-dependent repair of microlesions that occur in the muscle sarcolemma. Of the seven C2 domains in dysferlin, only C2A is reported to bind both Ca(2)(+) 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 Ca(2)(+) and phospholipid. Structural and thermodynamic analyses are consistent with the canonical C2A domain as a Ca(2)(+)-dependent, phospholipid-binding domain, whereas C2Av1 would likely be Ca(2)(+)-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 Ca(2)(+)-regulated effector interactions, an activity that would be essential in its role as a mediator of membrane repair.
PDB ID: 4IHBDownload
MMDB ID: 116044
PDB Deposition Date: 2012/12/18
Updated in MMDB: 2013/12
Experimental Method:
x-ray diffraction
Resolution: 2.044  Å
Source Organism:
Similar Structures:
Biological Unit for 4IHB: monomeric; determined by author
Molecular Components in 4IHB
Label Count Molecule
Protein (1 molecule)
1
Dysferlin(Gene symbol: DYSF)
Molecule annotation
Chemicals (10 molecules)
1
10
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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