Visualizing single-stranded nucleic acids in solution. Issue 9 (29th December 2016)

• Record Type: Journal Article
• Authors: Plumridge, Alex; Meisburger, Steve P.; Pollack, Lois
• Is Part Of: Nucleic acids research. Volume 45:Issue 9(2017)
• Page Start: e66
• Page End: e66
• Publication Date: 2016-12-29
• Subjects: Nucleic acids -- Periodicals; Molecular biology -- Periodicals; 572.805
• DOI: 10.1093/nar/gkw1297
• Languages: English
• ISSNs: 0305-1048

Abstract

Abstract: Single-stranded nucleic acids (ssNAs) are ubiquitous in many key cellular functions. Their flexibility limits both the number of high-resolution structures available, leaving only a small number of protein–ssNA crystal structures, while forcing solution investigations to report ensemble averages. A description of the conformational distributions of ssNAs is essential to more fully characterize biologically relevant interactions. We combine small angle X-ray scattering (SAXS) with ensemble-optimization methods (EOM) to dynamically build and refine sets of ssNA structures. By constructing candidate chains in representative dinucleotide steps and refining the models against SAXS data, a broad array of structures can be obtained to match varying solution conditions and strand sequences. In addition to the distribution of large scale structural parameters, this approach reveals, for the first time, intricate details of the phosphate backbone and underlying strand conformations. Such information on unperturbed strands will critically inform a detailed understanding of an array of problems including protein–ssNA binding, RNA folding and the polymer nature of NAs. In addition, this scheme, which couples EOM selection with an iteratively refining pool to give confidence in the underlying structures, is likely extendable to the study of other flexible systems.