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Volume 272, Number 14, Issue of April 4, 1997 pp. 8946-8956
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

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Demonstration of Coiled-Coil Interactions within the Kinesin Neck Region Using Synthetic Peptides
IMPLICATIONS FOR MOTOR ACTIVITY

(Received for publication, December 4, 1996, and in revised form, January 15, 1997)

Brian Tripet ^§ , Ronald D. Vale ^¶ and Robert S. Hodges ^§

From the  Department of Biochemistry and the ^§ Medical Research Council Group in Protein Structure and Function, University of Alberta, Edmonton, Alberta T6G 2H7, Canada and the ^¶ Howard Hughes Medical Institute and Departments of Pharmacology and Biochemistry/Biophysics, University of California, San Francisco, California 94143

Kinesin is a dimeric motor protein that can move for several micrometers along a microtubule without dissociating. The two kinesin motor domains are thought to move processively by operating in a hand-over-hand manner, although the mechanism of such cooperativity is unknown. Recently, a ~50-amino acid region adjacent to the globular motor domain (termed the neck) has been shown to be sufficient for conferring dimerization and processive movement. Based upon its amino acid sequence, the neck is proposed to dimerize through a coiled-coil interaction. To determine the accuracy of this prediction and to investigate the possible function of the neck region in motor activity, we have prepared a series of synthetic peptides corresponding to different regions of the human kinesin neck (residues 316-383) and analyzed each peptide for its respective secondary structure content and stability. Results of our study show that a peptide containing residues 330-369 displays all of the characteristics of a stable, two-stranded -helical coiled-coil. On the other hand, the NH₂-terminal segment of the neck (residues ~316-330) has the capacity to adopt a -sheet secondary structure. The COOH-terminal residues of the neck region (residues 370-383) are not -helical, nor do they contribute significantly to the overall stability of the coiled-coil, suggesting that these residues mark the beginning of a hinge located between the neck and the extended -helical coiled coil stalk domain. Interestingly, the two central heptads of the coiled-coil segment in the neck contain conserved, "non-ideal" residues located within the hydrophobic core, which we show destabilize the coiled-coil interaction. These residues may enable a portion of the coiled-coil to unwind during the mechanochemical cycle, and we present a model in which such a phenomenon plays an important role in kinesin motility.

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