Crystal Structure of the KIF5C Motor Domain With ADP
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This is a default text for your page Crystal Structure of the KIF5C Motor Domain With ADP. You may include any references to papers as in: the use of JSmol in Proteopedia [1] or to the article describing Jmol [2] to the rescue. ContentsNucleotide Pocket ConfigurationSwitch II and the neck-linker remain arranged similarly to ATP-like kinesin states, but switch I is shifted outward. This displacement rotates helix α3, moving L9 away from the pocket and disrupting the Arg191–Asp232 Mg-stabiliser. Without this stabiliser, Mg-ADP becomes inherently unstable, priming the motor for microtubule-stimulated nucleotide exchange. Contrast With MT-Bound ConformationsWhen KIF5C binds GTP-state GMPCPP microtubules, the motor undergoes a coordinated conformational tightening, switch I closes, α4 rotates inward, L11 elongates to wedge between α4 and α6, and the neck-linker begins docking. These transitions are absent in the ADP structure and define the rigour-like, strong-binding state required for rapid ADP release. Functional Relevance of L11L11, flexible and undocked in the ADP state, emerges as a central determinant of microtubule nucleotide-state sensing. Mutations in L11 abolish KIF5C’s preference for GTP-state microtubules and reduce MT-activated ATPase activity. ConclusionThe ADP structure provides a mechanistic baseline, clarifying how GTP-state microtubule recognition reshapes the KIF5C motor into its force-generating form. Because GTP-state lattices are enriched in axons relative to dendrites, this structural preference directly explains why KIF5C selectively enters axons and not dendrites. Accordingly, the ADP-bound conformation represents a primed intermediate that supports polarised neuronal transport upon recognition of the appropriate microtubule substrate.
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