The directional preference of kinesin motors is specified by an element outside of the motor catalytic domain.
Members of the kinesin superfamily share a similar motor catalytic domain yet move either toward the plus end (e.g., conventional kinesin) or the minus end (e.g., Ncd) of microtubules. The structural features that determine the polarity of movement have remained enigmatic. Here, we show that kinesin's catalytic domain (316 residues) in a dimeric construct (560 residues) can be replaced with the catalytic domain of Ncd and that the resultant motor moves in the kinesin direction. We also demonstrate that this chimera does not move processively over many tubulin subunits, which is similar to Ncd but differs from the highly processive motion of conventional kinesin. These findings reveal that the catalytic domain contributes to motor processivity but does not control the polarity of movement. We propose that a region adjacent to the catalytic domain serves as a mechanical transducer that determines directionality.
Case
R B
RB
Department of Pharmacology, University of California, San Francisco 94143, USA.
Pierce
D W
DW
Hom-Booher
N
N
Hart
C L
CL
Vale
R D
RD
D000251:Adenosine Triphosphatases / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D004330:Drosophila; D029721:Drosophila Proteins; D004926:Escherichia coli; D006801:Humans; D016547:Kinesins / Q000737:chemistry* / Q000502:physiology*; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000502:physiology
D029721:Drosophila Proteins; D011993:Recombinant Fusion Proteins; C066696:ncd protein, Drosophila; D000251:Adenosine Triphosphatases; D016547:Kinesins