4IHB

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

Summary for 4IHB

• Entry DOI: 10.2210/pdb4ihb/pdb
• Related: 2DMH 3L9B 4IQH
• Descriptor: Dysferlin, FORMIC ACID, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: beta sandwich, type ii c2 domain, muscular dystrophy, membrane protein, membrane repair, plasma membrane
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane, sarcolemma; Single-pass type II membrane protein: O75923
• Total number of polymer chains: 6
• Total formula weight: 89216.40

Authors

Sutton, R.B.,Fuson, K.L. (deposition date: 2012-12-18, release date: 2013-12-18, Last modification date: 2023-09-20)

Primary citation

Fuson, K.,Rice, A.,Mahling, R.,Snow, A.,Nayak, K.,Shanbhogue, P.,Meyer, A.G.,Redpath, G.M.,Hinderliter, A.,Cooper, S.T.,Sutton, R.B.
Alternate Splicing of Dysferlin C2A Confers Ca(2+)-Dependent and Ca(2+)-Independent Binding for Membrane Repair.
Structure, 22:104-115, 2014

PubMed Abstract: 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.

PubMed: 24239457
DOI: 10.1016/j.str.2013.10.001

Experimental method

X-RAY DIFFRACTION (2.044 Å)