7U4A

Crystal Structure of Zika virus xrRNA1 mutant

Summary for 7U4A

• Entry DOI: 10.2210/pdb7u4a/pdb
• Descriptor: RNA (70-MER), MAGNESIUM ION (3 entities in total)
• Functional Keywords: xrrna, viral rna, flavivirus, rna
• Biological source: Zika virus
• Total number of polymer chains: 1
• Total formula weight: 23350.21

Authors

Thompson, R.D.,Carbaugh, D.L.,Nielsen, J.R.,Witt, C.,Meganck, R.M.,Rangadurai, A.,Zhao, B.,Bonin, J.P.,Nathan, N.T.,Marzluff, W.F.,Frank, A.T.,Lazear, H.M.,Zhang, Q. (deposition date: 2022-02-28, release date: 2023-09-06, Last modification date: 2025-03-19)

Primary citation

Thompson, R.D.,Carbaugh, D.L.,Nielsen, J.R.,Witt, C.M.,Faison, E.M.,Meganck, R.M.,Rangadurai, A.,Zhao, B.,Bonin, J.P.,Nicely, N.I.,Marzluff, W.F.,Frank, A.T.,Lazear, H.M.,Zhang, Q.
Lifetime of ground conformational state determines the activity of structured RNA.
Nat.Chem.Biol., 2025

PubMed Abstract: Biomolecules continually sample alternative conformations. Consequently, even the most energetically favored ground conformational state has a finite lifetime. Here, we show that, in addition to the three-dimensional (3D) structure, the lifetime of a ground conformational state determines its biological activity. Using hydrogen-deuterium exchange nuclear magnetic resonance spectroscopy, we found that Zika virus exoribonuclease-resistant RNA (xrRNA) encodes a ground conformational state with a lifetime that is ~10-10 longer than that of canonical base pairs. Mutations that shorten the apparent lifetime of the ground state without affecting its 3D structure decreased exoribonuclease resistance in vitro and impaired virus replication in cells. Additionally, we observed this exceptionally long-lived ground state in xrRNAs from diverse infectious mosquito-borne flaviviruses. These results demonstrate the biological importance of the lifetime of a preorganized ground state and further suggest that elucidating the lifetimes of dominant 3D structures of biomolecules may be crucial for understanding their behaviors and functions.

PubMed: 39939412
DOI: 10.1038/s41589-025-01843-1

Experimental method

X-RAY DIFFRACTION (3.15 Å)