- Cytoplasmic dynein is a motor protein complex found in eukaryotes that is essential to many cellular processes. With dynein being involved in mitosis, axonal transport and organelle transport, disruption of dynein function can lead to neurodegeneration and other diseases. The main function of dynein is transportation of cargo through the attachment of a cofactor or regulatory protein, like dynactin. Many of dynein’s functions are regulated by binding of dynein intermediate chain (IC) to dynactin p150. This interaction involves a single alpha helix (SAH) at the N-terminus of IC and the coiled-coil region (CC1B) on p150. Previous studies in the Barbar lab have shown that there is a secondary helix (H2) downstream of SAH that is structurally varied among the species of IC. This study looks closely at IC from Chaetomium thermophilum (CT), and experiments reveal that it has a weak H2 and substantially stronger binding to p150. The data from this study describe the role of H2 in binding and is the first to show direct interactions between H2 and p150. A combination of results from isothermal titration calorimetry (ITC), circular dichroism (CD) and nuclear magnetic resonance (NMR) are used to map the binding site of CT IC on p150.
Key Words: Cytoplasmic dynein, dynein intermediate chain, dynactin p150, secondary helix, intermediate chain and p150 binding