New Folding Pattern of P150 and “Anntena” for Dynein Binding

Abstract

Dynactin is known to be a regulator of cytoplasmic dynein and play a part in intracellular transport. Dynactin is a large complex composed of multiple subunits including p150, p50 and Arp1, and has a characteristic architecture. Sidearm domain of dynactin is essential for binding to dynein and microtubule, but the structural detail of the domain is poorly understood due to its intricate organization. Here, by electron microscopy of the nanogold-labeled or the truncated mutants of human dynactin complex, the location of each domain of the largest subunit p150 was identified. We rediscovered the filamentous structure at the very tip of sidearm as a newly named “antenna”, which is comprised of two anti-parallel coiled-coil structures and crucial for dynein-binding. Furthermore, the composition of the globular head which is important for microtubule-binding is also renewed as the complex of the two discontinuous regions. These findings provide the clues for understanding dynactin functions and its molecular mechanism, especially as a regulator of dynein.