Fig. 6: Kap3-dependent activation of Kif3 by adaptor binding to the β-hairpin motif.
From: Regulation of kinesin-2 motility by its β-hairpin motif
a, Top, size-exclusion chromatogram of reconstituted Kif3AB–Kap3 complex in the presence of either APCARM (green) or APCARM-Mut (L395Y K399E K441E L437Y R440E, gray). Bottom, SDS–PAGE of size-exclusion chromatography fractions. Traces for APCARM and APCARM-Mut alone shown in Extended Data Fig. 4a. b, Example kymographs of Kif3AB-Kap (Alexa-Fluor-647-labeled Kif3A) in the presence of microtubules and APCARM or APCARM-Mut. c, AlphaFold3 model of APCARM in complex with Kif3AB–Kap3. Conserved APCARM residues at the interface are shown as black spheres and annotated (mutated in APCARM-Mut). APCARM occludes the Kif3A β-hairpin. d, Equivalent view to c, with the autoinhibited Kif3A motor domain binding site overlaid, showing steric clash with APCARM. The APCARM and Kif3A motor domain are shown in surface representation. e, Schematic model of kinesin-2 activation. Isolated Kif3 favors a compact autoinhibited conformation in which the β-hairpin motifs and C-terminal coiled coil interact with the motor domains, sequestering the motor domains from the microtubule. Binding of a cargo adaptor, exemplified here by APCARM, occludes the β-hairpin motif, promoting an extended activated conformation in which the motor domains are free to drive processive motility along the microtubule.
