7KVU

Crystal structure of Squash RNA aptamer in complex with DFHBI-1T

Summary for 7KVU

• Entry DOI: 10.2210/pdb7kvu/pdb
• Descriptor: Squash RNA aptamer, MAGNESIUM ION, POTASSIUM ION, ... (5 entities in total)
• Functional Keywords: fluorogenic aptamer, adenine riboswitch, rna
• Biological source: synthetic construct
• Total number of polymer chains: 1
• Total formula weight: 27521.64

Authors

Truong, L.,Ferre-D'Amare, A.R. (deposition date: 2020-11-28, release date: 2022-01-19, Last modification date: 2023-10-18)

Primary citation

Truong, L.,Kooshapur, H.,Dey, S.K.,Li, X.,Tjandra, N.,Jaffrey, S.R.,Ferre-D'Amare, A.R.
The fluorescent aptamer Squash extensively repurposes the adenine riboswitch fold.
Nat.Chem.Biol., 18:191-198, 2022

PubMed Abstract: Squash is an RNA aptamer that strongly activates the fluorescence of small-molecule analogs of the fluorophore of green fluorescent protein (GFP). Unlike other fluorogenic aptamers, isolated de novo from random-sequence RNA, Squash was evolved from the bacterial adenine riboswitch to leverage its optimized in vivo folding and stability. We now report the 2.7-Å resolution cocrystal structure of fluorophore-bound Squash, revealing that while the overall fold of the riboswitch is preserved, the architecture of the ligand-binding core is dramatically transformed. Unlike previously characterized aptamers that activate GFP-derived fluorophores, Squash does not harbor a G-quadruplex, sandwiching its fluorophore between a base triple and a noncanonical base quadruple in a largely apolar pocket. The expanded structural core of Squash allows it to recognize unnatural fluorophores that are larger than the simple purine ligand of the parental adenine riboswitch, and suggests that stable RNA scaffolds can tolerate larger variation than has hitherto been appreciated.

PubMed: 34937911
DOI: 10.1038/s41589-021-00931-2

Experimental method

X-RAY DIFFRACTION (2.68 Å)