Activation of Calcineurin Involves a Folding Upon Binding Event
| Autor: | Tori M. Dunlap, Trevor P. Creamer, Farai I. Rusinga, Terrence E. Lester, David D. Weis, A. Keith Dunker, Julie Rumi-Masante |
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| Rok vydání: | 2011 |
| Předmět: |
0303 health sciences
biology Calmodulin Chemistry fungi Phosphatase Biophysics food and beverages Active site 3. Good health Domain (software engineering) Cell biology Calcineurin Turn (biochemistry) Folding (chemistry) 03 medical and health sciences 0302 clinical medicine Biochemistry biology.protein 030217 neurology & neurosurgery Function (biology) 030304 developmental biology |
| Zdroj: | Biophysical Journal. 100(3) |
| ISSN: | 0006-3495 |
| DOI: | 10.1016/j.bpj.2010.12.236 |
| Popis: | Calcineurin (CaN) is a highly-conserved, ubiquitous Ser/Thr phosphatase that plays vital roles in memory development and retention, cardiac growth, and immune system activation. Alterations in the regulation of CaN contributes to disorders such as Alzheimer's disease, Down syndrome, autoimmune disorders and cardiac hypertrophy. The regulation of CaN function is not well understood at the molecular level. CaN is inactive until bound by calmodulin (CaM). We will present evidence that CaM binds to a 95 residue disordered regulatory domain in CaN. The binding of CaM to CaN results in the regulatory domain folding. Folding of the regulatory domain in turn causes an autoinhibitory domain located C-terminal to the regulatory domain to be ejected from CaN's active site. This binding-induced disorder-to-order transition is responsible for the activation of CaN by CaM. |
| Databáze: | OpenAIRE |
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