General Information

Research Interests

My research is focused on understanding the molecular basis of cell motility. Motor proteins are molecular machines that can convert the energy from ATP hydrolysis into force and motion. Myosin consists of a large superfamily of actin-based motor proteins that are involved in a wide variety of cell motility processes such as muscle contraction, organelle transport, and cell division (see myosin family tree below). Although myosin motors have a well conserved structural core, they have very different biochemical properties. Thus, small changes in structure appear to have profound effects on the biochemical properties of myosin motors. The long-term goal of my research program is to understand the basic mechanism of energy transduction used by all myosin motors and to determine how different members of the myosin superfamily have fine tuned their biochemical and structural properties to perform specific cellular functions.

Biophysical properties of myosin. A combination of genetic engineering and fluorescence spectroscopic methods are used to examine dynamic structural changes in myosin. Examining specific conformational changes in myosin will reveal important details about how myosin binds to actin, and how myosin generates force and motion using the energy from ATP hydrolysis.

Enzymatic properties of non-muscle myosins. Another goal of my research is to express and purify various non-muscle myosins and examine their enzymatic properties using transient kinetic methods. Characterizing the enzymatic cycle of these non-muscle myosins will lead to a better understanding of their cellular functions.

Regulation of non-muscle myosins. It is unclear how many non-muscle myosins are turned on and off in the cell. Another goal of my research is to characterize different mechanisms of regulation of non-muscle myosins, including ligand-induced structural changes, phosphorylation-induced structural changes, and interactions with other regulatory proteins that affect the biophysical properties of myosin.

Education

• B.S., Exercise Science, Indiana University, Bloomington, IN, 1991
• M.S., Exercise Physiology, University of Wyoming, Laramie, WY, 1996
• Ph.D., Molecular Physiology and Biophysics, University of Vermont, Burlington, VT, 2000- Mentor: Christopher Berger, Ph.D.
• Postdoctoral Fellow, University of Pennsylvania School of Medicine, Department of Physiology, 2000-2003 - Mentor: H. Lee Sweeney, Ph.D.

Courses Taught

• Human Anatomy and Physiology
• Cell Biology Seminar
• Physiology Lab

• Biophysics

• Biochemistry

• BIOL 6000/8000C01- Fluorescence Spectroscopy

Current Funding

American Heart Association, Scientist Development Grant, Mechanism of energy transduction in myosin. Christopher M. Yengo, Principle Investigator

NIH R03. Enzymatic and motor properties of myosin III. Christopher M. Yengo, Principle Investigator. Collaborators: Beth Burnside and Adrea Dose (UC Berkeley)

Selected Recent Publications

1)      Sun, M., Rose, M., Ananthanarayanan, S.K., Jacobs, D.J., and Yengo, C.M.  (2008). Characterization of the pre force-generation state in the actomyosin cross-bridge cycle. Proc. Natl. Acad. Sci. USA (In Press).

2)      Dosé, A.C., Ananthanarayanan, S., Moore, J.E., Burnside, B., and Yengo, C.M. (2008). The kinase domain alters the kinetic properties of the myosin IIIA motor. Biochemistry  47, 2485-2496.

3)      Yengo, C.M., Ananthanarayanan, S.K., Brosey, C.A.,  Mao, S.,  and Tyska, M.J. (2008). Human deafness mutation E385D disrupts the mechanochemical coupling and subcellular targeting of myosin-1a. Biophys. J.(Biofast letter), 94, L5-L7.

4)      Alyounes, D., Doran, T., Yengo, C.M., Lu, Q and Gonsalves, K. (2007). Development of Polymeric Micro/Nanostructures For Gene Delivery”, MRS Symposium FF e- Proceedings, 1019-FF05-13.

5)   Juncadella, I.J., Garg, R., Ananthanarayanan, S.K., Yengo, C.M., and Anguita, J. (2007). T-cell signaling pathways inhibited by the tick saliva immunosuppressor, Salp15. FEMS Immunol. Med. Microbiol. 49, 433-438.

6)      Dosé, A.C., Ananthanarayanan, S., Moore, J.E., Burnside, M.B. and Yengo, C.M. (2007).  Kinetic mechanism of human myosin IIIA.  J. Biol. Chem. 282, 216-231.

7)      Garg, R., Juncadella, I.J., Ramamoorthi, N., Ashish, F., Ananthanarayanan, S., Thomas, V., Rincon, M., Krueger, J.K., Fikrig, E., Yengo, C.M. and Anguita, J. (2006). Cutting edge: CD4 is the receptor for the tick saliva immunosuppressor, Salp15.  The Journal of Immunology177, 6579-6583.

8)      Sun, M., Oakes, J.L., Ananthanarayanan, S.K., Hawley, K.H., Tsien, R.Y., Adams, S.R., and Yengo, C.M. (2006). Dynamics of the upper 50 kDa domain of myosin V examined with fluorescence resonance energy transfer. J. Biol. Chem. 281, 5711-5717.

9)     Menetrey J., Bahloul A., Wells A.L., Yengo C.M., Morris C.A., Sweeney H.L., Houdusse A. (2005). The structure of the myosin VI motor reveals the mechanism of directionality reversal. Nature 435, 779-785.

10)      Wallace, K.N., Dolan, A.C., Seiler, C., Smith, E.M., Yusuff, S., Chaille-Arnold, L., Judson, B., Sierk, R., Yengo, C., Sweeney, H.L., Pack, M. (2005). Mutation of smooth muscle myosin causes invasion and cystic expansion of the zebrafish intestine. Dev. Cell 8, 717-726.

11)  Ramamurthy, B., Yengo, C.M., Straight, A.F., Mitchison, T.J., and Sweeney, H.L. Kinetic mechanism of blebbistatin inhibition of nonmuscle myosin IIB. (2004) Biochemistry 43, 14832-14839.

12)  Yengo, C.M. and Sweeney, H.L. (2004).  Functional role of loop 2 in myosin V.  Biochemistry 43, 2605-2612.

13)  Chakrabarty, T, Yengo, C.M., Sweeney, H.L. and Selvin, P.  (2003) Does the S2 rod of Myosin II uncoil upon two-headed binding to actin? A leucine-zippered HMM study. Biochemistry 42, 12886-92

14)  Coureux, P.D.,  Wells, A.L., Ménétrey, J., Yengo, C.M., Morris, C.A., Sweeney, H.L. and Houdusse, A. (2003) A structural state of the myosin V motor without bound nucleotide. Nature 425, 419-423.

15)  Yengo, C.M., De La Cruz, E.M., Safer, D., Ostap, E.M., and Sweeney, H.L.  (2002). Kinetic characterization of the weak binding states of myosin V. Biochemistry 41, 8508-8517.

16)  Yengo, C.M., De La Cruz, E.M., Chrin, L., and Berger, C.L. (2002) Actin-induced closure of the actin binding cleft of smooth muscle myosin. J. Biol. Chem. 277, 24114-24119.

17)  Yengo, C.M. and Berger, C.L.  (2002). Fluorescence resonance energy transfer in acto-myosin complexes.  Results and Problems in Cell Differentiation 36, 21-30.

18)  Yengo, C.M., Chrin, L., Rovner, A.S. and Berger, C.L. (2000) Tryptophan 512 is sensitive to structural changes in the rigid relay loop of smooth muscle myosin during the MgATPase cycle. J. Biol. Chem. 275, 25481-25487.

19)  Yengo, C.M., Chrin, L.R., and Berger, C.L.  Interaction of Lys-553 of myosin with the C-terminus and DNAse I binding loop of actin examined by fluorescence resonance energy transfer. (2000) J. Structural Biology 131,187-196.

20)  Yengo, C.M., Chrin, L., Rovner, A.S. and Berger, C.L.  (1999). Intrinsic tryptophan fluorescence identifies specific conformational changes at the actomyosin interface upon actin-binding and ADP-release.  Biochemistry 38, 14515-14523.

21)  Yengo, C.M., Fagnant, P.M., Chrin, L., Rovner, A.S. and Berger, C.L.  (1998). Smooth muscle myosin mutants containing a single tryptophan reveal molecular interactions at the actin-binding interface.  Proc. Natl. Acad. Sci. U.S.A. 95, 12944-12940.