Dimerization of mammalian kinesin-3 motors results in superprocessive motion.
The kinesin-3 family is one of the largest among the kinesin superfamily and its members play important roles in a wide range of cellular transport activities, yet the molecular mechanisms of kinesin-3 regulation and cargo transport are largely unknown. We performed a comprehensive analysis of mammalian kinesin-3 motors from three different subfamilies (KIF1, KIF13, and KIF16). Using Forster resonance energy transfer microscopy in live cells, we show for the first time to our knowledge that KIF16B motors undergo cargo-mediated dimerization. The molecular mechanisms that regulate the monomer-to-dimer transition center around the neck coil (NC) segment and its ability to undergo intramolecular interactions in the monomer state versus intermolecular interactions in the dimer state. Regulation of NC dimerization is unique to the kinesin-3 family and in the case of KIF13A and KIF13B requires the release of a proline-induced kink between the NC and subsequent coiled-coil 1 segments. We show that dimerization of kinesin-3 motors results in superprocessive motion, with average run lengths of ∼10 μm, and that this property is intrinsic to the dimeric kinesin-3 motor domain. This finding opens up studies on the mechanistic basis of motor processivity. Such high processivity has not been observed for any other motor protein and suggests that kinesin-3 motors are evolutionarily adapted to serve as the marathon runners of the cellular world.
Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109.
Virupakshi
V
Soppina
Stephen R
SR
Norris
Aslan S
AS
Dizaji
Matt
M
Kortus
Sarah
S
Veatch
Michelle
M
Peckham
Kristen J
KJ
Verhey
D000818:Animals; D005075:Biological Evolution; D001692:Biological Transport / Q000502:physiology; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry*; D002522:Chlorocebus aethiops; D019281:Dimerization; D031541:Fluorescence Resonance Energy Transfer; D016547:Kinesins / Q000737:chemistry*; D007700:Kinetics; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000378:metabolism*; D008958:Models, Molecular
D002352:Carrier Proteins; D016547:Kinesins
helical plot; intracellular transport; microtubule; molecular motor