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 R01. Enzymatic and motor properties of myosin III. Christopher
M. Yengo, Principle Investigator. Collaborators: Beth Burnside and Adrea Dose (UC Berkeley)
Open Postdoctoral Position
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.
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