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Lab Positions Available Shared Resources Arts and Sciences Chemistry and Biochemistry OSBP Biophysics Courses Center for RNA Biology GUARDD

Mark P. Foster Professor, Associate Chair Chemistry and Biochemistry The Ohio State University 484 West 12th Ave, Columbus, OH 43210 Office: 734 Riffe Building phone: (614) 292-1377 email: Foster.281@osu.edu B.S. University of Illinois, 1987 Ph.D. University of Utah, 1993 Postdoctoral Fellow, The Scripps Research Institute, 1993-1997 Research area: Structural Biology, Biomolecular NMR Spectroscopy. Research Interests: Protein and nucleic acid structure and dynamics, molecular recognition, signal transduction, enzyme catalysis, computational methods, 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, nucleic acids (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 spectrometers operating at 600 and 800 MHz, housed in a 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, mass spectrometry and computation. 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 nucleic acid binding proteins. Interactions between proteins and nucleic acids are central to fundamental biological processes such as transcription, translation and catalysis. Our laboratory is studying the solution structure of nucleic acid binding proteins in several categories: (1) DNA-binding transcription factors. The objective of these studies is to understand how specificity in protein-protein and protein-DNA interactions allow for the coordinated transcription of specific genes. (2) RNA-binding regulatory proteins. A number of interesting proteins interact with specific elements in the 5' leader regions of the mRNAs of nascently transcribed genes. These interactions are used by cells to regulate the translation of the encoded proteins and transcription of the genes. (3) DNA recombinases. These enzymes catalyze recombination of DNA duplexes by catalyzing strand cleavage and coordinating the rearrangement of the cleaved DNA strands via a Holliday junction. (4) RNase P. This is a ribonucleoprotein complex responsible for the maturation of tRNAs by cleaving nascently transcribed pre-tRNA genes. In eukaryotes, this enzyme consists of one catalytic RNA subunit and several protein subunits. We are working to determine the structures of several of the protein components in order to understand their role in catalysis. 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, we have a limited understanding of 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. We have been studying the dynamic behavior of two classes of enzymes: (1) a metallo-hydrolase and (2) a DNA recombinase.

SELECTED PUBLICATIONS:

Kleckner IR, Foster MP. "GUARDD: User-friendly MATLAB software for rigorous analysis of CPMG RD NMR data." (2012) J Biomol NMR 52:11-22. doi: 10.1007/s10858-011-9589-y

Kleckner IR, Gollnick P, Foster MP. "Mechanisms of Allosteric Gene Regulation by NMR Quantification of μs-ms Protein Dynamics." (2012) J Mol Biol 415(2): 372-381. doi: 10.1016/j.jmb.2011.11.019

Crowe BL, Bohlen CJ, Wilson RC, Gopalan V, Foster MP. "Assembly of the Complex between Archaeal RNase P Proteins RPP30 and Pop5." (2011) Archaea 2011: Article ID 891531. doi:10.1155/2011/891531, (PDF)

Chen WY, Xu Y, Cho IM, Oruganti SV, Foster MP, Gopalan V. "Cooperative RNP assembly: complementary rescue of structural defects by protein and RNA subunits of archaeal RNase P." (2011) J Mol Biol. 411(2):368-83.doi:10.1016/j.jmb.2011.05.012 (PubMed)

Wilson RC, Smith AM, Fuchs RT, Kleckner IR, Henkin TM, Foster MP. "Tuning Riboswitch Regulation through Conformational Selection." (2011) J Mol Biol 405(4):926-38. doi:j.jmb.2010.10.056, (PDF)

Kleckner IR, Foster MP. "An Introduction to NMR-based Approaches for Measuring Protein Dynamics." (2010) BBA - Proteins and Proteomics. Special Issue: Protein Dynamics.1841(8):942-968 (http://dx.doi.org/10.1016/j.bbapap.2010.10.012)

Sachleben JR, McElroy CA, Gollnick P, Foster MP. "Mechanism for pH-dependent gene regulation by amino-terminus-mediated homooligomerization of Bacillus subtilis anti-trp RNA-binding attenuation protein." (2010) Proc Natl Acad Sci U S A 107(35):15385-90 doi: 10.1073/pnas.1004981107

Xu Y, Amero CD, Pulukkunat DK, Gopalan V, Foster MP. "Solution structure of an archaeal RNase P binary protein complex: formation of the 30-kDa complex between Pyrococcus furiosus RPP21 and RPP29 is accompanied by coupled protein folding and highlights critical features for protein-protein and protein-RNA interactions." (2009) J Mol Biol. 393(5):1043-55. (PDF, http://dx.doi.org/10.1016/j.jmb.2009.08.068; PMC2782587)

Amero CD, Byerly DW, McElroy CA, Simmons A, Foster MP. "Ligand-induced changes in the structure and dynamics of Escherichia coli peptide deformylase." (2009) Biochemistry. 48(32):7595-607. DOI: 10.1021/bi900600b (PDF, SI). Addendum.

Amero CD, Boomershine WP, Xu Y, Foster M. "Solution structure of Pyrococcus furiosus RPP21, a component of the archaeal RNase P holoenzyme, and interactions with its RPP29 protein partner." (2008) Biochemistry. 47(45):11704-10. DOI: 10.1021/bi8015982 (PDF, html)

Kamadurai HB, Jain R and Foster MP, "Crystallization and structure determination of the core-binding domain of bacteriophage lambda integrase." (2008) Acta Crystallographica F, 64(6):470-473. (PDF, doi:10.1107/S174430910801381X)

Amero CD, Arnold JJ, Moustafa IM, Cameron CE, and Foster MP, "Identification of the oriI-binding site of poliovirus 3C protein by NMR spectroscopy." (2008) J Virol, 82(9):4363-70, PMID: 18305026. (PubMed, doi:10.1128/JVI.02087-07, PDF)

Kamadurai HB, Foster MP, "DNA recognition via mutual-induced fit by the core-binding domain of bacteriophage lambda integrase." (2007) Biochemistry, 46(49):13939-47. (PubMed, PDF) DOI: 10.1021/bi700974t

Subramaniam S, Kamadurai HB, Foster MP, "Trans Cooperativity by a Split DNA Recombinase: The Central and Catalytic Domains of Bacteriophage Lambda Integrase Cooperate in Cleaving DNA Substrates When the Two Domains Are not Covalently Linked." (2007) J Mol Biol. 370(2):303 - 314. (PubMed, PDF) doi:10.1016/j.jmb.2007.04.024

Foster MP, McElroy CA, Amero CD, "Solution NMR of Large Molecules and Assemblies." (2007) Biochemistry 46(2):331 - 340. (Pubmed, PDF)

McElroy CA, Manfredo A, Gollnick P, Foster MP, "Thermodynamics of tryptophan-mediated activation of the trp RNA-binding attenuation protein." (2006) Biochemistry 45(25):7844-53. (Pubmed, PDF)

Wilson RC, Bohlen CJ, Foster MP, Bell CE, "Structure of Pfu Pop5, an archaeal RNase P protein." (2006) Proc Natl Acad Sci U S A 103(4):873-8. (Pubmed, PDF)

Boomershine WP, McElroy CA, Tsai HY, Wilson RC, Gopalan V, Foster MP, "Structure of Mth11/Mth Rpp29, an essential protein subunit of archaeal and eukaryotic RNase P." (2003) Proc Natl Acad Sci U S A. 100(26), 15398-403. (Pubmed, PDF)

Subramaniam S, Tewari AK, Nunes-Duby SE, Foster MP, "Dynamics and DNA Substrate Recognition by the Catalytic Domain of Lambda Integrase." (2003) J Mol Biol 329(3), 423-439. (Pubmed, PDF)

Kamadurai HB, Subramaniam S, Jones RB, Green-Church KB, Foster MP, "Protein folding coupled to DNA binding in the catalytic domain of bacteriophage lambda integrase detected by mass spectrometry." (2003) Protein Science 12(3), 620-6.(PubMed, PDF)


McElroy C, Manfredo A, Wendt A, Gollnick P, Foster M. "TROSY-NMR of the 91 kDa TRAP Protein Reveals Allosteric Control of a Gene Regulatory Protein by Ligand-Altered Flexibility." (2002) J. Mol. Biol. 323, 463-47. ( PubMed, PDF)