Dynein achieves processive motion using both stochastic and coordinated stepping
Open Access
- 8 January 2012
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Structural & Molecular Biology
- Vol. 19 (2), 193-200
- https://doi.org/10.1038/nsmb.2205
Abstract
The processivity of myosins and kinesins has been well studied, but how the dynein homodimer achieves continuous motion is unknown. Two-dimensional analysis of labeled, DNA-dimerized dynein demonstrates that dynein has an unusual stepping pattern and can alternate between stochastic- and tension-based stepping to achieve processivity. Processivity, the ability of single molecules to move continuously along a track, is a fundamental requirement of cargo-transporting molecular motors. Here, we investigate how cytoplasmic dynein, a homodimeric, microtubule-based motor, achieves processive motion. To do this, we developed a versatile method for assembling Saccharomyces cerevisiae dynein heterodimers, using complementary DNA oligonucleotides covalently linked to dynein monomers labeled with different organic fluorophores. Using two-color, single-molecule microscopy and high-precision, two-dimensional tracking, we find that dynein has a highly variable stepping pattern that is distinct from all other processive cytoskeletal motors, which use 'hand-over-hand' mechanisms. Uniquely, dynein stepping is stochastic when its two motor domains are close together. However, coordination emerges as the distance between motor domains increases, implying that a tension-based mechanism governs these steps. This plasticity may allow tuning of dynein for its diverse cellular functions.Keywords
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