Hahn Hye Jee, Pashkova Natalya, Cianfrocco Michael A, Weisman Lois S
Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI, USA.
Life Sciences Institute, University of Michigan , Ann Arbor, MI, USA.
J Cell Biol. 2025 Jul 7;224(7). doi: 10.1083/jcb.202408006. Epub 2025 May 16.
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.
肌球蛋白V类分子Myo2对于芽殖酵母中的细胞器运输至关重要。它与货物的结合由介导附着和释放的衔接蛋白调节。Vac17是一种液泡特异性衔接蛋白，将Myo2与液泡膜蛋白Vac8连接起来，并在液泡遗传过程中Myo2-Vac17-Vac8复合物的组装和解聚中起关键作用。通过遗传学、冷冻电镜和结构预测，我们发现Vac17在两个不同的位点与Myo2相互作用，而不是在单个界面上。同样，过氧化物酶体衔接蛋白Inp2与Myo2的两个不同区域结合，其中一个区域与Vac17结合位点重叠。这些发现支持了一种“把手”模型，即货物衔接蛋白占据Myo2尾部的多个表面，这可能增强了马达与货物的结合，并对马达募集提供了额外的调控。
