RT Journal Article
A1 Hahn, Hye Jee
A1 Pashkova, Natalya
A1 Cianfrocco, Michael A.
A1 Weisman, Lois S.
T1 Cargo adaptors use a handhold mechanism to engage with myosin V for organelle transport
JF Journal of Cell Biology
JO J Cell Biol
YR 2025
DO 10.1083/jcb.202408006
OP e202408006
VO 224
IS 7
SN 0021-9525
AB 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.
RD 5/24/2025
UL https://doi.org/10.1083/jcb.202408006