title: The two motor domains of KIF3A/B coordinate for processive motility and move at different speeds.
abstract: KIF3A/B, a kinesin involved in intraflagellar transport and Golgi trafficking, is distinctive because it contains two nonidentical motor domains. Our hypothesis is that the two heads have distinct functional properties, which are tuned to maximize the performance of the wild-type heterodimer. To test this, we investigated the motility of wild-type KIF3A/B heterodimer and chimaeric KIF3A/A and KIF3B/B homodimers made by splicing the head of one subunit to the rod and tail of the other. The first result is that KIF3A/B is processive, consistent with its transport function in cells. Secondly, the KIF3B/B homodimer moves at twice the speed of the wild-type motor but has reduced processivity, suggesting a trade-off between speed and processivity. Third, the KIF3A/A homodimer moves fivefold slower than wild-type, demonstrating distinct functional differences between the two heads. The heterodimer speed cannot be accounted for by a sequential head model in which the two heads alternate along the microtubule with identical speeds as in the homodimers. Instead, the data are consistent with a coordinated head model in which detachment of the slow KIF3A head from the microtubule is accelerated roughly threefold by the KIF3B head.
authors.affiliation: Department of Bioengineering, The Pennsylvania State University, University Park, Pennsylvania 16802, USA. wohbio@engr.psu.edu
authors.forename: Yangrong
authors.initials: Y
authors.lastname: Zhang
authors.forename: William O
authors.initials: WO
authors.lastname: Hancock
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001692:Biological Transport; D055592:Biophysical Phenomena; D001703:Biophysics; D002465:Cell Movement; D002850:Chromatography, Gel; D018076:DNA, Complementary / Q000378:metabolism; D019281:Dimerization; D004591:Electrophoresis, Polyacrylamide Gel; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D016547:Kinesins / Q000737:chemistry*; D007700:Kinetics; D018715:Microscopy, Video; D008870:Microtubules / Q000378:metabolism; D008957:Models, Genetic; D020409:Molecular Motor Proteins; D008969:Molecular Sequence Data; D009068:Movement; D010957:Plasmids / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D018076:DNA, Complementary; C087415:KIF3A protein, human; C095899:KIF3B protein, human; D020409:Molecular Motor Proteins; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D016547:Kinesins