Open AccessStructural snapshots of the kinesin‐2 OSM‐3 along its nucleotide cycle: implications for the ATP hydrolysis mechanism
Author(s) -
Varela Paloma F.,
Che Mélanie,
Velours Christophe,
Verhey Kristen J.,
Ménétrey Julie,
Gigant Benoît
Publication year - 2021
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1002/2211-5463.13101
Subject(s) - kinesin , atp hydrolysis , microtubule , atpase , subfamily , nucleotide , motor protein , linker , chemistry , microbiology and biotechnology , cyclic nucleotide binding domain , biochemistry , biology , biophysics , enzyme , gene , computer science , operating system
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 .