Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), Gif-sur-Yvette, France.
Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, USA.
FEBS Open Bio. 2021 Mar;11(3):564-577. doi: 10.1002/2211-5463.13101. Epub 2021 Feb 28.
Motile kinesins are motor proteins that translocate along microtubules as they hydrolyze ATP. They share a conserved motor domain which harbors both ATPase and microtubule-binding activities. An ATP hydrolysis mechanism involving two water molecules has been proposed based on the structure of the kinesin-5 Eg5 bound to an ATP analog. Whether this mechanism is general in the kinesin superfamily remains uncertain. Here, we present structural snapshots of the motor domain of OSM-3 along its nucleotide cycle. OSM-3 belongs to the homodimeric kinesin-2 subfamily and is the Caenorhabditis elegans homologue of human KIF17. OSM-3 bound to ADP or devoid of a nucleotide shows features of ADP-kinesins with a docked neck linker. When bound to an ATP analog, OSM-3 adopts a conformation similar to those of several ATP-like kinesins, either isolated or bound to tubulin. Moreover, the OSM-3 nucleotide-binding site is virtually identical to that of ATP-like Eg5, demonstrating a shared ATPase mechanism. Therefore, our data extend to kinesin-2 the two-water ATP hydrolysis mechanism and further suggest that it is universal within the kinesin superfamily. PROTEIN DATABASE ENTRIES: 7A3Z, 7A40, 7A5E.
动力蛋白是沿着微管运动的马达蛋白，在水解 ATP 时会发生位移。它们共享一个保守的马达结构域，该结构域同时具有 ATP 酶和微管结合活性。基于与 ATP 类似物结合的 kinesin-5 Eg5 的结构，提出了一个涉及两个水分子的 ATP 水解机制。该机制是否在驱动蛋白超家族中普遍存在仍不确定。在这里，我们展示了沿核苷酸循环的 OSM-3 马达结构域的结构快照。OSM-3 属于同源二聚体的 kinesin-2 亚家族，是人类 KIF17 的 Caenorhabditis elegans 同源物。OSM-3 与 ADP 结合或不含有核苷酸时，表现出与 ADP-驱动蛋白类似的特征，具有对接的颈部接头。当与 ATP 类似物结合时，OSM-3 采用与几种 ATP 样驱动蛋白相似的构象，无论是单独存在还是与微管结合。此外，OSM-3 的核苷酸结合位点与 ATP 样 Eg5 的几乎相同，证明存在共享的 ATP 酶机制。因此，我们的数据将双水分子 ATP 水解机制扩展到 kinesin-2，并进一步表明它在驱动蛋白超家族中是普遍存在的。蛋白质数据库条目：7A3Z、7A40、7A5E。
