Structural insights into the assembly of a monomeric class V myosin.
Structural insights into the assembly of a monomeric class V myosin.
复制标题
对单体 V 类肌球蛋白组装的结构见解。
DOI：
10.1073/pnas.1403205111
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发表时间：
2014
影响因子：
11.1
通讯作者：
Rayment,Ivan
中科院分区：
文献类型：
--
作者：
Rayment,Ivan
Motor proteins are a vital contributor to life, where they manifest themselves in the directed movement of organisms, in cell division, and in the transport of organelles, proteins, and nucleic acids. The “Big Three” superfamilies of linear motor proteins consist of myosin, kinesin, and dynein, which move along actin or microtubules. Over the past 60 y, since the discovery of the sliding filament model for muscle contraction and the identification of myosin as the active component, considerable effort has been devoted to understanding the molecular properties of the motor domains that generate directed movement. In contrast, considerably less is known about the structural interactions of these motors with their partners, which is ironic because motors only exist to move or apply force to something! Not surprisingly, this is a rich area for investigation that is now yielding an understanding of not only the structural themes but also the regulation of motors by their cargoes. An example of this is seen in PNAS, where Shi et al.(1) reveal how the budding yeast myosin Myo4p, a class V myosin, interacts with its partners She3p and She2p to facilitate transport of mRNA. The report by Shi et al. provides structural insight into how cargo binding efficiently regulates this myosin through oligomerization rather than through a disruption of a direct head-tail inhibitory interaction as often seen in many myosins (2) and members of the kinesin superfamily (3, 4). In yeast, Myo4p transports∼ 20 types of mRNA molecules along actin cables to specific locations in the cytoplasm to generate local concentrations of the corresponding gene product. The mRNAs are targeted by specific cis-acting elements, which have been called “zip codes,” that are up to 100 nucleotides long. This process facilitates transport of mRNA to the daughter cell. There are two adapter proteins involved in this transport system, She2p and She3p. She2p is a tetramer that binds the mRNA zip code in the nucleus and once in the cytoplasm forms a complex with Myo4p and Shep3 (5, 6). She3p interacts with She2p and Myo4p, but also contains an additional binding site for the cotransport of tubular endoplasmic reticulum (ER) to the yeast bud (7). Myo4p belongs to the myosin V family, the members of which take characteristically long steps along the actin filament. Myo4p is an unusual myosin V because by itself it is not a processive motor, as are most other myosins in this class. Instead, it exists as a constitutive monomer instead of a dimer, where dimerization is needed to take long coordinated steps along actin (8, 9). Nonprocessivity in class V myosins has also been proposed for the second myosin V in yeast: Myo2p, a Drosophila myosin V, and human myosin Vc (10–12). It is well established that monomeric motors must work together to generate directed movement; thus, the initial question was whether this requires an organized oligomeric structure or whether it can be accomplished by multiple motors attached to the cargo that is being transported. Elegant work by Trybus and colleagues demonstrated that Myo4p forms a tight single-headed complex with She3p, which alone is not capable of processive movement and has no tendency to dimerize, but on addition of She2p forms a two-headed processive assembly (5, 13). Recent single-molecule in vitro reconstruction of the transport complex shows that mRNA is required to form a stable processive assembly at physiological ionic strength, and that increasing the number of zip codes on the mRNA increases the run length of the complex (14). This observation showed that
