Article
- The EMBO Journal (2004) 23, 1506 - 1515
- doi:10.1038/sj.emboj.7600164
Published online: 11 March 2004
Subject Categories:
An intramolecular interaction between the FHA domain and a coiled coil negatively regulates the kinesin motor KIF1A
Jae-Ran Lee1, Hyewon Shin1, Jeonghoon Choi1, Jaewon Ko1, Seho Kim1, Hyun Woo Lee1, Karam Kim1, Seong-Hwan Rho2, Jun Hyuck Lee2, Hye-Eun Song2, Soo Hyun Eom2 and Eunjoon Kim1
- National Creative Research Initiative Center for Synaptogenesis and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea
- Department of Life Science, Kwangju Institute of Science and Technology, Gwangju, Korea
Correspondence to:
Eunjoon Kim, National Creative Research Initiative Center for Synaptogenesis and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Kuseong-dong, Yuseong-ku, Daejeon 305-701, South Korea. Tel.: +82 42 869 2633; Fax: +82 42 869 2610; E-mail: kime@kaist.ac.kr
Received 15 October 2003; Accepted 16 February 2004
Abstract
Motor proteins not actively involved in transporting cargoes should remain inactive at sites of cargo loading to save energy and remain available for loading. KIF1A/Unc104 is a monomeric kinesin known to dimerize into a processive motor at high protein concentrations. However, the molecular mechanisms underlying monomer stabilization and monomer-to-dimer transition are not well understood. Here, we report an intramolecular interaction in KIF1A between the forkhead-associated (FHA) domain and a coiled-coil domain (CC2) immediately following the FHA domain. Disrupting this interaction by point mutations in the FHA or CC2 domains leads to a dramatic accumulation of KIF1A in the periphery of living cultured neurons and an enhancement of the microtubule (MT) binding and self-multimerization of KIF1A. In addition, point mutations causing rigidity in the predicted flexible hinge disrupt the intramolecular FHA–CC2 interaction and increase MT binding and peripheral accumulation of KIF1A. These results suggest that the intramolecular FHA–CC2 interaction negatively regulates KIF1A activity by inhibiting MT binding and dimerization of KIF1A, and point to a novel role of the FHA domain in the regulation of kinesin motors.
Keywords:
- coiled coil,
- FHA,
- kinesin,
- KIF1A,
- microtubule binding
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