4IQH
Crystal Structure Analysis of Dysferlin C2A variant 1 (C2Av1)
Summary for 4IQH
| Entry DOI | 10.2210/pdb4iqh/pdb |
| Related | 2DMH 3L9B 4IHB |
| Descriptor | Dysferlin (2 entities in total) |
| Functional Keywords | c2 domain, membrane repair, acidic phospholipid binding, peripheral membrane protein, membrane protein |
| Biological source | Homo sapiens (human) |
| Cellular location | Cell membrane, sarcolemma; Single-pass type II membrane protein: O75923 |
| Total number of polymer chains | 3 |
| Total formula weight | 42985.57 |
| Authors | Sutton, R.B.,Fuson, K.L. (deposition date: 2013-01-11, 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 Cited by 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: 24239457DOI: 10.1016/j.str.2013.10.001 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.764 Å) |
Structure validation
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