Mark P. Foster
|
Associate Professor
Phone: 614-292-1377
Fax: 614-292-6773
email: foster.281@osu.edu
Webpage: Foster Homepage |
Research Interests:
Protein and nucleic acid structure and dynamics, molecular recognition,
signal transduction, enzyme catalysis, computational methods, small
molecule design, NMR methodology.
Understanding how the structure and mobility of biological molecules
influence their function is one of the most exciting and rewarding research
objectives in biochemistry, and is the main focus of my laboratory's
efforts. Biological processes are coordinated via complex molecular
interactions involving proteins, nucleicacids (DNA, RNA) and small molecules.
These molecules are not rigid, but rather undergo dynamic conformational
changes to achieve their functions.
High-resolution NMR spectroscopy is ideally suited to our principle
objective of understanding these motions, as it is the only method that
allows us to study both the structural and dynamic properties of macromolecules
at atomic resolution. Our group enjoys access to outstanding NMR facilities,
including one of the world's most powerful spectrometers (operating
at 800 MHz) housed in the new state-of-the-art Structural Biology Center.
While NMR spectroscopy is one major research tool in the laboratory,
our projects are fundamentally multidisciplinary and collaborative,
merging components of molecular biology, protein engineering and biochemistry,
NMR spectroscopy, computation and synthetic chemistry. As a result,
members of the laboratory have the opportunity and are encouraged to
become competent in diverse creative approaches for solving biochemical
problems. Group members obtain rigorous training in basic research by
studying the fundamental principles that govern biomolecular function,
and emerge with scientific skills to pursue careers in either academics
or private industry.
Structure and function of proteins that regulate cell fate. Cells react
to external stimuli via a cascade of biomolecular interactions involving
cell-surface receptors, biological sensors, kinases, phosphatases and
signaling molecules that relay information from the surface to the interior
of the cell where internal conditions determine the appropriate response.
Responses can include inflammation (lysis), proliferation (growth and
division), quiescence (resting) or apoptosis (suicide). These responses
are often carried put the transcription or degradation of specific proteins.
Malfunction of signaling processes can have dire consequences: cancer,
muscular dystrophy and autoimmune diabetes are well-recognized disorders
that result from improper cellular response. Our work seeks to reveal
how proteins recognize the appropriate signal and pass it on down the
next step in the cascade.
Enzyme structure and dynamics. Enzymes catalyze chemical reactions
by binding the appropriate substrates in a conformation that lowers
the energetic activation barrier, and then releases the products, at
the appropriate rate. While the structures of many different enzymes
are known, little is known about the molecular motions that enable enzymes
to carry out their function. This lack of understanding severely limits
our ability to design drugs to specifically inhibit the enzymes, or
to design new enzymes to carry out novel chemistries. We seek to understand
of the mode of action of select enzymes by characterizing their solution
behavior (structure and dynamics) and to examine the effects of inhibitor
and substrate binding.
Publications
Selected publications from the last 5 years:
Foster, M. P., McElroy CA, Amero CD. (2007) "Solution NMR of large molecules and assemblies." Biochemistry 46(2), 331-40. Review.
McElroy CA, Manfredo A, Gollnick P, Foster, M. P.. (2006) "Thermodynamics of tryptophan-mediated activation of the trp RNA-binding attenuation protein." Biochemistry. 45(25), 7844- 53.
Wilson RC, Bohlen CJ, Foster, M. P., Bell CE. (2006) "Structure of Pfu Pop5, an archaeal RNase P protein." Proc Natl Acad Sci U S A. 103(4), 873-8.
Boomershine WP, McElroy CA, Tsai HY, Wilson RC, Gopalan V, Foster,
M.P.
(2003) "Structure of Mth11/Mth Rpp29, an essential protein subunit
of archaeal and eukaryotic RNase P.", Proc Natl Acad Sci U
S A. 100(26), 15398-403.
Subramaniam, S., Tewari, A.K., Nunes-Duby, S., and Foster,
M.P. (2003) "Dynamics
and DNA substrate recognition by the catalytic domain of lambda integrase." J.
Mol. Biol. 329, 423-39.
Boomershine, W.P., Stephen Raj, M.L., Gopalan, V., and Foster,
M.P. (2003) "Preparation of uniformly labeled NMR samples in Escherichia
coli under the tight control of the araBAD promoter: expression of an
archaeal homolog of the RNase P Rpp29 protein." Protein Expr.
Purif. 28, 246-51.
Murray, T.A., Foster, M.P., and Swenson, R.P. (2003) "Mechanism
of flavin mononucleotide cofactor binding to the Desulfovibrio vulgaris
flavodoxin. 2. Evidence for cooperative conformational changes involving
tryptophan 60 in the interaction between the phosphate- and ring-binding
subsites." Biochemistry 42, 2317-27.
Kamadurai, H.B., Subramaniam, S., Jones, R.B., Green-Church, K.B.,
and Foster, M.P. (2003) "Protein folding coupled to DNA binding
in the catalytic domain of bacteriophage lambda integrase detected by
mass spectrometry." Protein Sci. 12, 620-6.
McElroy, C.A., A. Manfredo, A. Wendt, P. Gollnick and Foster,
M.P.,
(2002). "TROSY-NMR of the 91 kDa TRAP Protein Reveals Allosteric
Control of a Gene Regulatory Protein by Ligand-Altered Flexibility." J.
Mol. Biol. 323, 463-47.
Byerly, D.W., C.A. McElroy and Foster, M.P., (2002) “Mapping the Surface
of Escherichia coli Peptide Deformylase by NMR with Organic Solvents.”. Protein
Science 11,1850-3.
Kim, H.-J. and Foster, M.P., (2002).“Characterization of Ad5 E3-14.7K,
an Adenoviral Inhibitor of Apoptosis: Structure, Oligomeric State and
Metal Binding.” Protein Science 11, 1117-28.
Kamaduriai, H, S. Subramaniam, A.K. Tewari and Foster,
M.P., (2002)
“DNA-Induced protein conformational changes monitored by mass spectrometry.”Protein
Science 11 Suppl. 1, 447.
