Structural study of slective cargo transport by unconventional myosins

肌球蛋白的货物运输对于正常的细胞现象是必不可少的。我们对肌球蛋白-X尾部结构域进行了一系列的结构和生化研究，该结构域由MyTH4和FERM结构域与其特定的载体--Netrin受体DCC(在结直肠癌中缺失)组成。结果，我们发现了DCC多肽的一种意想不到的结合模式，这与以前在Radioxin/黏附分子复合体中发现的结合方式不同。此外，我们揭示了MyTH4-ferm结构域与微管蛋白C末端酸性尾巴之间的直接相互作用，并确定MyTH4结构域的一个带正电荷的斑块是微管蛋白结合区。我们还证明了DCC和整合素结合都干扰微管结合，DCC结合干扰整合素结合。我们的结果提供了肌球蛋白-X促进与货物和微管的交替双重结合的分子基础。

The Cargo transportation by myosins is essential for proper cell phenomena. We peformed a series of structural and biochemicalstudies of the myosin-X tail domain , consisting of MyTH4 and FERM domains in complex with its specific cargo, a netrin receptor DCC (deleted in colorectal cancer). As the result, we found an unexpected binding mode of the DCC peptide, which is distinct from previously reported associations found in radixin/adhesion molecule complexes.Moreover, we revealed direct interactions between the MyTH4-FERM domain and tubulin C-terminal acidic tails, and identified a positively charged patch of the MyTH4 domain as a tubulin binding region. We also demonstrated that both DCC and integrin bindings interfere with microtubule binding and that DCC binding interferes with integrin binding. Our results provide the molecular basis by which myosin-X facilitates alternative dual binding to cargos and microtubules.