Kinesin-1 is an essential anterograde microtubule motor protein. The core kinesin motor is a homodimer of two heavy chains; N-terminal motor domains hydrolyze ATP and walk along microtubules, while a long elongated coiled-coil stalk and an intrinsically disordered C-terminal tail region bind cargos. Kinesin autoinhibition is key to preventing futile ATP consumption and occurs, at least in part, through direct interactions between N-terminal motor domains and C-terminal inhibitory motifs. Despite significant advances in our understanding of kinesin walking, little is known about the kinesin-1 conformational landscape of the stalk and tail domains. Here, we apply solution-based biophysical analysis tools to study conformational changes in kinesin-1, with full rotational freedom, and in response to changes in ionic strength, mutations, and the presence of microtubules. This has allowed us to uncover the inherent flexibility in kinesin-1, which gives insights into autoinhibition and the regulation of intracellular transport.
Smith et al. (Tue,) studied this question.