Department of Neuroscience, Cell Biology, & Anatomy
5.212A Research Building 17Route
: 1069 |
(409) 772-1309 | Fax:
(409) 747-2187 | email@example.com
Affiliation: Sealy Center for Structural Biology & Molecular Biophysics
Education and Training
PhD in Physiology & Biophysics, University of Chile, Santiago, Chile
Post-Doctoral in Physiology & Biophysics, University of Pennsylvania, Pennsylvania
Post-Doctoral in Physiology & Biophysics, Mayo Clinic, Rochester, Minneapolis
Single-molecule methods have emerged as powerful tools in life science
research. These techniques allow the detection and manipulation of
individual biological molecules and investigate, with unprecedented
resolution, their conformations and dynamics at the nanoscale level. In
my research I apply single-molecule techniques to biological problems
that are important for human diseases.
The goal of my current research is to elucidate
the precise molecular mechanisms by which the chaperones UNC-45 and
Hsp90 assist in the folding of the myosin head which is critical for
sarcomere assembly during development and repair of stress-induced
damage to sarcomeres in mature muscle. Developing an understanding of
these mechanisms is a problem at the core of muscle development and
Guided by our recent discoveries, we hypothesize
that during myosin assembly or repair, UNC-45 assists the myosin head
to attain its native conformation and subsequently locks it in a state
that prevents premature powerstrokes; this state is relieved by the
ubiquitous chaperone Hsp90 upon successful assembly into the sarcomere
or repair of myosin heads. My group recently devised novel approaches
to analyze myosin:chaperone interactions using a combination of
single-molecule atomic force microscopy, site specific fluorescence
probes and in vitro myosin motility techniques, that enable us
to study, for the first time, the effects of these chaperone proteins
on the myosin motor domain folding and function in mechanistic detail.
Our hypothesis, if confirmed, will represent a new
paradigm in the biology of myosins, with potential novel therapeutic
approaches not only for striated muscle disorders stemming from
mutations in sarcomeric proteins (skeletal myopathies and
cardiomyopathies), but also for the problem of tumor invasiveness.
Oberhauser, A., Monck, J.R., Balch, W.E. and Fernandez, J.M. Exocytotic fusion is activated by Rab3 peptides. Nature 360:270-273, 1992.
Oberhauser, A.F., Marszalek, P.E., Erickson, H.P., and Fernandez, J.M. The molecular elasticity of tenascin, an extracellular matrix protein. Nature 393:181-185, 1998.
Qian, F., Wei, W., Germino, G.G., and Oberhauser, A.F. The Nanomechanics of Polycystin-1 extracellular region. J. Biol. Chem. 280(49):40723-30, 2005.
Bullard, B., Garcia, T., Benes., V., Leake, M., Linke, W., and Oberhauser, A.F. The Molecular Elasticity of the Insect Flight Muscle Proteins Projectin and Kettin. Proc. Natl. Acad. Sci. 103(12) 4451-4456, 2006.
Kaiser, C.M., Bujalowski, P.J., Ma, L., Anderson, J., Epstein, H.F. and Oberhauser, A.F. Tracking UNC-45 chaperone-myosin interaction with a titin mechanical reporter. Biophys J. 102(9):2212-9, 2012.
Bujalowski, .PJ., Nicholls, P. and Oberhauser, A.F. UNC-45B chaperone: the role of its domains in the interaction with the myosin motor domain. Biophys J. 107(3):654-61, 2014.
Nicholls, P., Bujalowski, P.J., Epstein, H.F., Boehning, D.F., Barral, J.M. and Oberhauser, A.F. Chaperone-mediated reversible inhibition of the sarcomeric myosin power stroke. FEBS Lett. 588(21):3977-81, 2014.
Bujalowski, P.J., Nicholls, P., Barral, J.M. and Oberhauser, A.F. Thermally-induced structural changes in an armadillo repeat protein suggest a novel thermosensor mechanism in a molecular chaperone. FEBS Lett. 589(1):123-30, 2015.
Bujalowski PJ, Nicholls P, Garza E, and Oberhauser AF. The central domain of UNC-45 chaperone inhibits the myosin power stroke. FEBS Open Bio. 2017 Dec 10;8(1):41-48, 2018.
I. Gaziova; T. Moncrief; C. J. Christian; M. White; M. Villarreal; S. Powell; H. Qadota; G. M. Benian; A. F. Oberhauser. Mutational analysis of the structure and function of the chaperone domain of UNC-45B. bioRxiv 2020
Link to PubMed Publications