The actin bundling activity of actin bundling protein 34 is inhibited by calcium binding to the EF2
Highlights: • Wild-type ABP34 protein induces formation of actin bundles at low calcium concentrations, and this activity is diminished at higher calcium concentrations. • The actin bundling activity of ABP34 is activated when calcium ion is not bound to the protein through its EF2 calcium-binding motif. • The presence of calcium ion in the EF2 motif affects the stability and conformation of the EF-hand pair. Actin bundling protein 34 (ABP34) is the one of 11 actin-crosslinking proteins identified in Dictyostelium discoideum, a novel model organism for the study of actin-associated neurodegenerative disorders such as Alzheimer's disease and Huntington's disease. ABP34 localizes at the leading and trailing edges of locomotory cells, i.e., at the cell cortex, filopodia, and pseudopodia. Functionally, it serves to stabilize membrane-associated actin at sites of cell–cell contact. In addition, this small crosslinking protein is involved in actin bundle formation, and its bundling activity is regulated by the concentration of calcium ion. Several studies have sought to determine the mechanism underlying the calcium-regulated actin bundling activity of ABP34, but it remains unclear. Using several mutational and structural analyses, we revealed that calcium binding to the EF2 motif disrupts the inter-domain interaction between the N- and C-domains, thereby inhibiting the actin bundling activity of ABP34. This finding provides clues about the pathogenesis of neurodegenerative disorders related to actin bundling.
- OSTI ID:
- 23105540
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 503, Issue 3; Other Information: Copyright (c) 2018 Elsevier Inc. All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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