Alternate splicing of dysferlin C2A confers Ca²⁺-dependent and Ca²⁺-independent binding for membrane repair
| Autor: | Kerry, Fuson, Anne, Rice, Ryan, Mahling, Adam, Snow, Kamakshi, Nayak, Prajna, Shanbhogue, Austin G, Meyer, Gregory M I, Redpath, Anne, Hinderliter, Sandra T, Cooper, R Bryan, Sutton |
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| Rok vydání: | 2013 |
| Předmět: |
Models
Molecular endocrine system Molecular Sequence Data Membrane Proteins Muscle Proteins Crystallography X-Ray Recombinant Proteins Article Cell Line Protein Structure Tertiary Myoblasts Alternative Splicing Mice Sarcolemma Mutagenesis Site-Directed Animals Humans Regeneration Thermodynamics Calcium Amino Acid Sequence RNA Messenger Dysferlin Protein Binding |
| Zdroj: | Structure (London, England : 1993). 22(1) |
| ISSN: | 1878-4186 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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