Discovery-driven Science: a New Model for Cell Motility

Abstract

Movement is an essential characteristic of life. On the cellular level, it is powered by many different classes of motor proteins. Kinesins are one class of linear molecular motor proteins, which move on cytoskeletal tracks called microtubules. Conventional kinesins are dimeric molecules composed of several domains, including a motor domain which has a catalytic core that binds to a nucleotide (ATP or ADP). The nucleotide-bound state of kinesin during the motile cycle affects its neck position, a determinant of its direction of movement, and microtubule affinity. There are two types of motor protein movement: processive, in which the motor steps progressively along the cytoskeletal track without detaching, and nonprocessive, in which the motor detaches from the track after a single power stroke. Conventional kinesins move processively due to the dimerization of the two motor heads. The two heads are kept out of phase due to communication between the heads. Kar3, the kinesin of interest in this project, moves non-processively and is the only C-terminal motor protein found in budding yeast. Its functional form is a heterodimer with one of two non-catalytic polypeptides, Cik1 and Vik1. This project showcases Vik1 as the key to a novel model for motility due to the surprising discovery that the Vik1:microtubule interaction is influenced by the nucleotide-binding state of Kar3. There must be communication between Kar3 and Vik1 to cause Vik1’s release from the microtubule, as well as to allow the progression of microtubule-binding and, thus, movement along the microtubule.