Xiang Dong Li, Ph.D.

Academic Role: Research Assistant Professor

Faculty Appointment(s) In:
   Physiology

Function and Regulation of Unconventional Myosin Motor Protein

My broad research interests lie in how the components within a cell move to the right place at the right time. Unlike the prokaryotic cell, which largely consists of a single intracellular compartment surrounded by a plasma membrane, the eukaryotic cell has an elaborate internal membrane system, including a number of functionally distinct membrane-bounded compartments (organelles). Each organelle has a distinct set of enzymes and other specialized molecules, and thus distinct functions. Given the dimension and complexity of eukaryotic cells, the transport of components within them can not be solely dependent on diffusion. Indeed, maintenance of internal membrane systems and transportation of organelles both depend on a complex network of protein filaments called the cytoskeleton.  The cytoskeleton consists of three types of protein filaments: actin, microtubule, and intermediate filaments. Each filament interacts with a large number of accessory proteins. One type of accessory proteins is motor proteins, including dynein, kinesin, and myosin, that hydrolyze ATP to produce force and directed movement. I am particularly interested in myosins, which move along actin filaments.

My current research focuses on class V unconventional myosin, one of the most ancient members of the myosin superfamily, which is distributed from low eukaryotes, such as yeast, to high eukaryotes such as mammalian cells. The goal of my research is two-fold: to understand the molecular basis of class V myosin regulation and to clarify its function in intracellular trafficking.

Figure 1.  The predicted structure of myosin-Va based on its sequence.

Figure 2.The proposed model for the regulation of myosin-Va. (Left) The inhibited myosin-Va is in a folded conformation. At low Ca²⁺ conditions, GTD binds to the C-terminal end of the first long coiled-coil domain. Coil-2 to coil-5 region forms a compact structure that is visualized as a small globular domain. The binding of the motor domain to the GTD associated at the C-terminal end of the first coiled-coil stabilizes an isosceles triangle conformation, and prevents the conformational changes of motor domain during ATP turnover cycle, thus inhibiting the ATPase activity of motor domain.  (Right) The activated myosin-Va is in an extended conformation. High Ca²⁺ or cargo-binding interferences the interaction between GTD and head, thus disrupting the triangular shape.

Recent Publications

1. Xiang-dong Li,, Troy E. Rhodes, Reiko Ikebe, Taketoshi Kambara, Howard D. White and Mitsuo Ikebe (1998) Effects of mutations in the g-phosphate binding site of myosin on its motor function. Journal of Biological Chemistry 273(42): 27404-27411.
2. Xiang-dong Li, Junya Saito, Reiko Ikebe, Katsuhide Mabuchi, and Mitsuo Ikebe (2000) The interaction between the regulatory light chain domains on two heads is critical for regulation of smooth muscle myosin. Biochemistry 39(9): 2254-2260.
3. Yu Chen, Norio Takizawa, Jessica L Crowley, Sang W. Oh, Cheryl L. Gatto, Taketoshi Kambara, Osamu Sato, Xiang-dong Li, Mitsuo Ikebe, and Elizabeth J. Luna (2003) F-actin and myosin II binding domains in supervillin. Journal of Biological Chemistry  278:46094-46106
4. Xiang-dong Li and Mitsuo Ikebe. (2003) Two functional heads are required for full activation of smooth muscle myosin. Journal of Biological Chemistry 278: 29435-29441.
5. Xiang-dong Li, Katsuhide Mabuchi, Reiko Ikebe, and Mitsuo Ikebe (2004) Ca²⁺ induced activation of ATPase activity of myosin Va is accompanied with a large conformational change. Biochemical and Biophysical Research Communications 315: 538-545.
6. Xiang-dong Li, Reiko Ikebe, and Mitsuo Ikebe (2005) Activation of Myosin Va function by melanophilin, a specific docking partner of Myosin Va. Journal of Biological Chemistry 278: 29435-29441.
7. Xiang-dong Li^*, Hyun Suk Jung, Katsuhide Mabuchi, Roger Craig, and Mitsuo Ikebe (2006) The globular tail domain of myosin Va functions as an inhibitor of the myosin Va motor. Journal of Biological Chemistry 281:21789-21798  (This paper has been citied in “Faculty of 1000”).
8. Osamu Sato, Xiang-dong Li, and Mitsuo Ikebe (2007) Myosin Va becomes a low duty ratio motor in the inhibited form. Journal of Biological Chemistry 282:13228-13239.

9. Xiang-dong Li^*, Hyun Suk Jung, Qizhi Wang, Reiko Ikebe, Roger Craig, and Mitsuo Ikebe (2008) The globular tail domain puts on the brake to stop the ATPase cycle of the myosin Va. Proceedings of the National Academy of Sciences USA 105: 1140-1145 (This paper has been citied in “Faculty of 1000”).

* corresponding author.

Academic Background

1990, BS, East China University of Science and Technology
1993, MS, Shanghai Institute of Entomology, Chinese Academy of Science
1996, Ph.D., Shanghai Institute of Biochemistry, Chinese Academy of Science

Keywords: Signal Transduction, Cell Motility, Cytoskeleton

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