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Title: Crystal structure of a poly(rA) staggered zipper at acidic pH: evidence that adenine N1 protonation mediates parallel double helix formation

Journal Article · · Nucleic Acids Research
DOI:https://doi.org/10.1093/nar/gkw526· OSTI ID:1375924

We have solved at 1.07 Å resolution the X-ray crystal structure of a polyriboadenylic acid (poly(rA)) parallel and continuous double helix. Fifty-nine years ago, double helices of poly(rA) were first proposed to form at acidic pH. Here, we show that 7-mer oligo(rA), i.e. rA7, hybridizes and overlaps in all registers at pH 3.5 to form stacked double helices that span the crystal. Under these conditions, rA7 forms well-ordered crystals, whereas rA6 forms fragile crystalline-like structures, and rA5, rA8 and rA11 fail to crystallize. Our findings support studies from ~50 years ago: one showed using spectroscopic methods that duplex formation at pH 4.5 largely starts with rA7 and begins to plateau with rA8; another proposed a so-called ‘staggered zipper’ model in which oligo(rA) strands overlap in multiple registers to extend the helical duplex. While never shown, protonation of adenines at position N1 has been hypothesized to be critical for helix formation. Bond angles in our structure suggest that N1 is protonated on the adenines of every other rAMP–rAMP helix base pair. Lastly, our data offer new insights into poly(rA) duplex formation that may be useful in developing a pH sensor.

Research Organization:
Office of Scientific and Technical Information, Oak Ridge, TN (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER)
OSTI ID:
1375924
Journal Information:
Nucleic Acids Research, Vol. 44, Issue 17; ISSN 0305-1048
Publisher:
Oxford University PressCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 15 works
Citation information provided by
Web of Science

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Cited By (7)

Structural transitions in poly(A), poly(C), poly(U), and poly(G) and their possible biological roles journal November 2018
The effect of adenine protonation on RNA phosphodiester backbone bond cleavage elucidated by deaza-nucleobase modifications and mass spectrometry journal July 2019
Protonated nucleobases are not fully ionized in their chloride salt crystals and form metastable base pairs further stabilized by the surrounding anions journal June 2018
Adenine protonation enables cyclic-di-GMP binding to cyclic-GAMP sensing riboswitches journal July 2018
Protonated nucleobases are not fully ionized in their chloride salt crystals and form metastable base pairs further stabilized by the surrounding anions text January 2018
Protonated nucleobases are not fully ionized in their chloride salt crystals and form metastable base pairs further stabilized by the surrounding anions text January 2018
Influence of nucleotide modifications at the C2’ position on the Hoogsteen base-paired parallel-stranded duplex of poly(A) RNA journal August 2017

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