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Tertiary folds of the SL5 RNA from the 5' proximal region of SARS-CoV-2 and related coronaviruses.

Kretsch RC, Xu L, Zheludev IN, Zhou X, Huang R, Nye G, Li S, Zhang K, Chiu W, Das R
Proc Natl Acad Sci U S A 121 e2320493121 (2024)
Related entries: 8uyg, 8uyj, 8uyk, 8uyl, 8uym, 8uyp, 8uys

Cited: 1 times
EuropePMC logo PMID: 38427602

Abstract

Coronavirus genomes sequester their start codons within stem-loop 5 (SL5), a structured, 5' genomic RNA element. In most alpha- and betacoronaviruses, the secondary structure of SL5 is predicted to contain a four-way junction of helical stems, some of which are capped with UUYYGU hexaloops. Here, using cryogenic electron microscopy (cryo-EM) and computational modeling with biochemically determined secondary structures, we present three-dimensional structures of SL5 from six coronaviruses. The SL5 domain of betacoronavirus severe-acute-respiratory-syndrome-related coronavirus 2 (SARS-CoV-2), resolved at 4.7 Å resolution, exhibits a T-shaped structure, with its UUYYGU hexaloops at opposing ends of a coaxial stack, the T's "arms." Further analysis of SL5 domains from SARS-CoV-1 and MERS (7.1 and 6.4 to 6.9 Å resolution, respectively) indicate that the junction geometry and inter-hexaloop distances are conserved features across these human-infecting betacoronaviruses. The MERS SL5 domain displays an additional tertiary interaction, which is also observed in the non-human-infecting betacoronavirus BtCoV-HKU5 (5.9 to 8.0 Å resolution). SL5s from human-infecting alphacoronaviruses, HCoV-229E and HCoV-NL63 (6.5 and 8.4 to 9.0 Å resolution, respectively), exhibit the same coaxial stacks, including the UUYYGU-capped arms, but with a phylogenetically distinct crossing angle, an X-shape. As such, all SL5 domains studied herein fold into stable tertiary structures with cross-genus similarities and notable differences, with implications for potential protein-binding modes and therapeutic targets.

Articles - 8uye mentioned but not cited (1)

  1. research-article Tertiary folds of the SL5 RNA from the 5' proximal region of SARS-CoV-2 and related coronaviruses. Kretsch RC, Xu L, Zheludev IN, Zhou X, Huang R, Nye G, Li S, Zhang K, Chiu W, Das R. bioRxiv 2023.11.22.567964 (2023)




Related citations provided by authors (1)

  1. Tertiary folds of the SL5 RNA from the 5' proximal region of SARS-CoV-2 and related coronaviruses.. Kretsch RC, Xu L, Zheludev IN, Zhou X, Huang R, Nye G, Li S, Zhang K, Chiu W, Das R bioRxiv (2023)

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