DIRECTION DETERMINATION IN THE MINUS-END-DIRECTED KINESIN MOTOR NCD

Motor proteins of the kinesin superfamily transport intracellular carg o along microtubules. Although different kinesin proteins share 30-50% amino-acid identity in their motor catalytic cores, some move to the plus end of microtubules whereas others travel in the opposite directi on(1,2). Crystal structures of the Catalytic cores of conventional kin esin (a plus-end-directed motor involved in organelle transport) and n cd (a minus-end-directed motor involved in chromosome segregation) are nearly identical(3,4); therefore, the structural basis for their oppo site directions of movement is unknown. Here we show that the ncd 'nec k', made up of 13 class-specific residues next to the superfamily-cons erved catalytic core, is essential for minus-end-directed motility, as mutagenesis of these neck residues reverses the direction of ncd moti on. By solving the 2.5 Angstrom structure of a functional ncd dimer,we show that the ncd neck(a coiled-coil) differs from the corresponding region in the kinesin neck tan interrupted beta-strand)(5,6), although both necks interact with similar elements in the catalytic cores. The distinct neck architectures also confer different symmetries to the n cd and kinesin dimers and position these motors with appropriate direc tional bias on the microtubule.