Reference: Hahn HJ, et al. (2025) Cargo adaptors use a handhold mechanism to engage with myosin V for organelle transport. J Cell Biol 224(7)

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Abstract


Myo2, a class V myosin motor, is essential for organelle transport in budding yeast. Its association with cargo is regulated by adaptor proteins that mediate both attachment and release. Vac17, a vacuole-specific adaptor, links Myo2 to the vacuole membrane protein Vac8 and plays a key role in assembling and disassembling the Myo2-Vac17-Vac8 complex during vacuole inheritance. Using genetics, cryo-EM, and structure prediction, we find that Vac17 interacts with Myo2 at two distinct sites rather than a single interface. Similarly, the peroxisome adaptor Inp2 engages two separate regions of Myo2, one of which overlaps with a Vac17-binding site. These findings support a "handhold" model, in which cargo adaptors occupy multiple surfaces on the Myo2 tail, which likely enhances motor-cargo associations as well as provide additional regulatory control over motor recruitment.

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Journal Article
Authors
Hahn HJ, Pashkova N, Cianfrocco MA, Weisman LS
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