Biography

Xun Sun earned his Ph.D. under the guidance of Prof. Haw Yang at Princeton University. His Ph.D. work focused on elucidating how protein dynamics drive sequential biochemical reactions in non-ribosomal peptide synthetases using single-molecule Förster resonance energy transfer (FRET) and kinetic modeling. He then switched fields to solution nuclear magnetic resonance (NMR) spectroscopy and performed his postdoctoral research under the mentorships of Prof. Peter Wright and Prof. Jane Dyson at Scripps Research. His postdoctoral research involved probing the aggregation pathway of human transthyretin and studying how a phosphorylation-dependent switch regulates DNA binding of human p53. For his independent research in the Department of Biochemistry and Molecular Biology and the Sealy Center for Structural Biology and Molecular Biophysics at the University of Texas Medical Branch at Galveston, the Sun group combines biomolecular NMR, single-molecule FRET, and data-driven computational modeling to probe how protein dynamics are coupled with protein function or dysfunction in human health and disease. 

Research

1. Functional dynamics of intrinsically disordered motifs in cancer suppressor p53

Human p53 plays a central role in suppressing tumors, and its dysfunctional mutations are present in over 50% of human cancers. The full-length p53 consists of unstructured and structured domains and can form dimers or tetramers at physiological concentrations. The dynamic interactions among these domains are critical for p53 to function properly, including binding and releasing recognition-element DNAs in response to time-dependent post-translational modifications.  We aim to answer the following questions:

• How do unstructured motifs dynamically interact with structured DNA-binding domains in p53 dimers and tetramers? 
• How do oncogenic mutations and post-translational modifications influence the conformational ensemble of p53?

2. Role of conformational dynamics in antimicrobial biosynthesis

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a large class of natural products, including antimicrobial lantibiotics active against some multidrug-resistant bacteria. RiPP biosynthetic pathways are defined by sequential biochemical reactions to form modified peptides with highly regio- and stereo-specific chemical motifs.  The dynamic interactions between peptide substrates and biosynthetic enzymes are essential to drive the multistep biosynthesis of RiPPs. We are interested in probing the following questions:

• How do RiPP synthetases coordinate multiple conformations to drive sequential biochemical reactions?
• How are the regio- and stereo-specificities enforced for substrate peptides during RiPP biosynthesis?

Please check our group website for more information on open positions and current research opportunities.