Tianbing Xia, Ph.D.
Education and Professional Affiliations
B.S., Chemistry, Peking University
M.S., Physical/Structural Chemistry, Peking University
Ph.D., Biophysical Chemistry, University of Rochester
Post Doctorate Scholarship, California Institute of Technology
Member, American Chemical Society
Overview
Our research aim to understand the principles of molecular recognition, biomolecular structures, folding and dynamics, and more importantly, the correlations between structures, energetics, dynamics, and functions of important biomolecules. We are addressing these problems by interdisciplinary approaches, employing a battery of state-of-the-art methodologies from the fields of modern molecular biology, biochemistry, chemical physics, and synthetic chemistry. We are developing novel structural biology tools, particularly, ultrafast laser spectroscopy, combined with other traditional spectroscopy, to probe nucleic acid and protein structures, nucleic acid-protein interactions, and the central roles that these interactions play in regulating important biological processes.
Molecular recognition: Cultivating the Femto RNA Land!
Biological macromolecules are structurally dynamical by nature, and they sample an ensemble of conformations at different timescales on a landscape that is defined by their chemical identity and environment. One of our current research focuses is on developing femtosecond resolved laser spectroscopy as a novel structural biology tool to analyze the heterogeneous structural ensembles of interesting biomolecules, particularly the ruggedness of the conformational landscape of functional RNAs, DNAs, proteins, and their complexes. This approach provides unique and quantitative information on biological structures as an ensemble rather than a single static or averaged frame. We are trying to understand the principles of RNA and protein folding and the consequence of the complicate conformational landscape in molecular recognition, and the effects of ligand-induced changes in the landscape. Structural heterogeneity and conformational dynamics can have great influence on functionality. The knowledge will form the basis for understanding the fundamental principles of molecular recognition.
We are also using the ultrafast spectroscopy as one of the main tools to probe complex RNA-protein, DNA-protein, and protein-protein interactions, and elucidate their roles in high-order functional macromolecular assemblies. We have previously demonstrated that this unique approach is a powerful one for elucidating complex interaction networks. Correlating structure, energetics, dynamics, and functions is the key to obtain a coherent picture of biological functions. The fundamental mechanism of transcription antitermination by N protein of phage lambda has been a long-standing mystery in gene regulation. We will test our hypotheses of how precise conformational arrangements and interactions are communicated by the participating factors in the complicated transcription complex.
We are also interested in using combinatorial selection as an approach to analyze RNA-protein interactions systematically. Chemical diversity is one of the keys to expanding our repertoire of RNA-binding ligands. We will develop unnatural peptide ligands (e.g., D peptides) via approaches that combine the power of mRNA display-based selection and reflection selection against important RNA targets, including regulatory RNA structures from HIV. We hope to deduce the rules of RNA recognition by natural and unnatural ligands and use that knowledge to rationally design ligands with enhanced recognition specificity and affinity towards important RNA targets.
The long term goals of analyzing complex RNA structures and RNA-protein interactions is to enhance our understanding of molecular recognition and enable us to design better ligands to understand and ultimately control biological processes.
Selected Publications:
Jia Lu, Beena Mary Kadakkuzha, Liang Zhao, Martin Fan, Xin Qi, and Tianbing Xia, “Dynamic Ensemble View of the Conformational Landscape of HIV-1 TAR RNA and Allosteric Recognition”, Biochemistry, 50, 5042-5057 (2011). Featured Article on Global Medical Discovery.
Xin Qi and Tianbing Xia, “Structure, dynamics, and mechanism of the lead-dependent ribozyme”, BioMolecular Concepts, 2, 305-314 (invited review, 2011).
Xiaojun Zhang, Sang Won Lee, Liang Zhao, Tianbing Xia, and Peter Z. Qin, “Conformational distributions at the N-Peptide/boxB RNA interface studied using site-directed spin labeling”, RNA, 16, 2474-2483 (2010).
Xin Qi, Tianbing Xia, and Richard W. Roberts, “Acridine-N Peptide Conjugates Display Enhanced Affinity and Specificity for boxB RNA Targets”, Biochemistry, 49, 5782-5789 (2010).
Niyati Jain, Liang Zhao, John D. Liu, and Tianbing Xia, “The Heterogeneity and Dynamics of Ligand Recognition Mode in Purine-Sensing Riboswitches”, Biochemistry, 49, 3703-3714 (2010).
Sang Won Lee, Liang Zhao, Arthur Pardi, and Tianbing Xia, “Ultrafast Dynamics Show That the Theophylline and 3-Methylxanthine Aptamers Employ a Conformational Capture Mechanism for Binding Their Ligands”, Biochemistry, 49, 2943-2951 (2010).
Liang Zhao and Tianbing Xia, “Probing RNA Conformational Dynamics and Heterogeneity using Femtosecond Time-resolved Fluorescence Spectroscopy”, Methods, 49, 128-135 (invited review, 2009).
Beena Mary Kadakkuzha, Liang Zhao, and Tianbing Xia, “Conformational Distribution and Ultrafast Base Dynamics of Leadzyme”, Biochemistry, 48, 3807-3809 (2009).
Tianbing Xia, “Taking Femtosecond Snapshots of RNA Conformational Dynamics and Complexity”, Curr. Opin. Chem. Biol., 12, 604-611 (invited review, 2008).
John D. Liu, Liang Zhao, and Tianbing Xia, “The Dynamic Structural Basis of Differential Enhancement of Conformational Stability by 3’- and 5’-Dangling Ends in RNA”, Biochemistry, 47, 5962-5975 (2008).
Neelaabh Shankar, Tianbing Xia, Scott D. Kennedy, Thomas R. Krugh, David H. Mathews, and Douglas H. Turner, “NMR Reveals Absence of Hydrogen Bonding in Adjacent UU and AG Mismatches in an Isolated Internal Loop from Ribosomal RNA”, Biochemistry 46, 12665-12678 (2007).
Liang Zhao and Tianbing Xia, “Direct Revelation of Multiple Conformations in RNA by Femtosecond Dynamics”, J. Am. Chem. Soc., 129, 4118-4119 (2007).
Tianbing Xia, Chaozhi Wan, Richard W. Roberts, and Ahmed H. Zewail, “RNA-Protein Recognition: Single-Residue Ultrafast Dynamical Control of Structural Specificity and Function”, Proc. Natl. Acad. Sci USA. 102, 13013-13018 (2005).
Chaozhi Wan, Tianbing Xia, Hans-Christian Becker, and Ahmed H. Zewail, “Ultrafast Unequilibrated Charge Transfer: A New Channel in the Quenching of Fluorescent Biological Probes”, Chem. Phys. Lett., 412, 158-163 (2005).
Yuhong Wang, J. Spence Baskin, Tianbing Xia, and Ahmed H. Zewail, “Human Myoglobin Recognition of Oxygen: Dynamics of the Energy Landscape”, Proc. Natl. Acad. Sci USA. 101, 18000-18005 (2004).
Amisha Kamal, JK., Tianbing Xia, Samir Kumar, Liang Zhao, and Ahmed H. Zewail, “Enzyme functionality and solvation of Subtilisin Carlsberg: from hours to femtosecond”, Chem. Phys. Lett., 387, 209-215 (2004).
Liang Zhao, Samir Kumar Pal, Tianbing Xia, and Ahmed H. Zewail, “Dynamics of ordered water in interfacial enzyme recognition: bovine pancreatic phospholipase A2”, Angew. Chemie. Int. Ed., 43, 60-63 (2004).
Ryan J. Austin, Tianbing Xia, Jinsong Ren, Terry T. Takahashi, and Richard W. Roberts, “Differential modes of recognition in N peptide-boxB complexes”, Biochemistry, 42, 14957-14967 (2003).
Samir Kumar Pal, Liang Zhao, Tianbing Xia, and Ahmed H. Zewail, “Site and Sequence Selective Ultrafast Hydration of DNA”, Proc. Natl. Acad. Sci USA. 100, 13746-13751 (2003).
Tianbing Xia, Adam Frankel, Terry T. Takahashi, Jinsong Ren, and Richard W. Roberts, “Context and conformation dictate function in a transcription antitermination switch”, Nat. Struct. Biol., 10, 812-819 (2003).
Tianbing Xia, Hans-Christian Becker, Chaozhi Wan, Adam Frankel, Richard W. Roberts, and Ahmed H. Zewail, “The RNA-protein Complex: Direct probing of the interfacial recognition dynamics and its correlation with biological functions”, Proc. Natl. Acad. Sci USA. 100, 8119-8123 (2003).
Ryan J. Austin, Tianbing Xia, Jinsong Ren, Terry Takahashi, and Richard W. Roberts, “Designed Arginine-Rich RNA-Binding Peptides with Picomolar Affinity”, J. Am. Chem. Soc. 124, 10966-10967 (2002).
Jeffrey E. Barrick, Terry T. Takahashi, Jinsong Ren, Tianbing Xia, and Richard W. Roberts, “Large libraries reveal diverse solutions to an RNA recognition problem”, Proc. Natl. Acad. Sci. USA 98, 12374-12378 (2001).
Mark E. Burkard, Tianbing Xia, and Douglas H. Turner, “Thermodynamics of RNA Internal Loops with a Guanosine-Guanosine Pair Adjacent to Another Noncanonical Pair”, Biochemistry 40, 2478-2483 (2001).
Bin Tian, Robert J. White, Tianbing Xia, Stephen Welle, Douglas H. Turner, Michael B. Mathews, and Charles A. Thornton, “Expanded CUG repeat RNAs form hairpins that activate the double-stranded RNA-dependent protein kinase PKR”, RNA, 6, 79-87 (2000).
Tianbing Xia, John SantaLucia, Jr., Mark E. Burkard, Ryszard Kierzek, Susan J. Schroeder, Xiaoqi Jiao, Christopher Cox, and Douglas H. Turner, “Thermodynamic Parameters for an Expanded Nearest-Neighbor Model for Formation of RNA Duplexes with Watson-Crick Base Pairs”, Biochemistry 37, 14719-14735 (1998).
Tianbing Xia, Jeffrey J. McDowell, and Douglas H. Turner, “Thermodynamics of Non-symmetric Tandem Mismatches Adjacent to GC Base Pairs in RNA” Biochemistry 36, 12486-12497 (1997).
Book Chapters
Tianbing Xia, “RNA Conformational Dynamics: Perspectives from Ultrafast Spectroscopy”, in “Ultrafast Biomolecular Dynamics at the Nanoscale”, ed. Stefan Haacke and Irene Burghardt (Coming in 2012, Pan Stanford Publishing).
Tianbing Xia, David H. Mathews, and Douglas H. Turner, “Thermodynamics of RNA Secondary Structure Formation”, in vol. 6 of “Comprehensive Natural Products Chemistry”, ed. D.G. Söll, S. Nishimura, & P.B. Moore, pp. 21-47 (1999). Reprinted in paperback as “RNA” in 2001 (Elsevier Science).
- Updated: February 6, 2006
