Characterizing the unfolded states of RNA, DNA, and proteins.

Polyelectrolyte model of ssDNA

Figure 1. Polyelectrolyte model for single-stranded DNA [3].

The recent discovery of new biological roles for intrinsically disordered proteins and single-stranded nucleic acids calls for renewed attention to structure and dynamics of the unfolded state ensembles. Through the combination of two techniques, single-molecule Förster Resonance Energy Transfer (smFRET) and SAXS, we have measured the polymer properties of single-stranded RNA, DNA [1,3], and chemically-unfolded proteins [2]. I contributed to these projects in two ways: first by performing SAXS experiments, and second by developing polyelectrolyte models (Fig. 1) to bridge the SAXS and smFRET data and extract statistical parameters, such as the persistence length [1] and effective charge [3].

Research Articles

[1]

Chen H*, Meisburger SP*, Pabit SA, Sutton JL, Webb WW, Pollack L. 2012. Ionic strength-dependent persistence lengths of single-stranded RNA and DNA. Proc. Natl. Acad. Sci. U.S.A. 109(3): 799-804. (*equal contribution). PMID: 22203973, DOI: 10.1073/pnas.1119057109

[2]

Yoo TY*, Meisburger SP*, Hinshaw J*, Pollack L, Haran G, Sosnick TR, Plaxco K. 2012. Small-angle X-ray scattering and single-molecule FRET spectroscopy produce highly divergent views of the low-denaturant unfolded state. J. Mol. Biol. 418(3-4): 226-36. (*equal contribution) PMID: 22306460, DOI: 10.1016/j.jmb.2012.01.016

[3]

Meisburger SP, Sutton JL, Chen H, Pabit SA, Kirmizialtin S, Elber R, Pollack L. 2013. Polyelectrolyte properties of single stranded DNA measured using SAXS and single-molecule FRET: beyond the wormlike chain model. Biopolymers 99: 1032-45. PMID: 23606337, DOI: 10.1002/bip.22265