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| Title | Tertiary folds of the SL5 RNA from the 5' proximal region of SARS-CoV-2 and related coronaviruses. |
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| Journal, issue, pages | Proc Natl Acad Sci U S A, Vol. 121, Issue 10, Page e2320493121, Year 2024 |
| Publish date | Mar 5, 2024 |
 Authors | Rachael C Kretsch / Lily Xu / Ivan N Zheludev / Xueting Zhou / Rui Huang / Grace Nye / Shanshan Li / Kaiming Zhang / Wah Chiu / Rhiju Das /   |
| PubMed 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 ...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. |
 External links | Proc Natl Acad Sci U S A / PubMed:38427602 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 4.7 - 9.1 Å |
| Structure data | EMDB-42801, PDB-8uye:  EMDB-42802: BtCoV-HKU5 5' proximal stem-loop 5, conformation 3 EMDB-42805, PDB-8uyg: EMDB-42808, PDB-8uyj: EMDB-42809, PDB-8uyk: EMDB-42810, PDB-8uyl: EMDB-42811, PDB-8uym: EMDB-42816, PDB-8uyp: EMDB-42818, PDB-8uys:  EMDB-42819: SARS-CoV-2 5' proximal stem-loop 5 and 6 with SL5c extended  EMDB-42820: SARS-CoV-2 5' proximal stem-loop 5 and 6 with SL5b extended  EMDB-42821: SARS-CoV-2 5' proximal stem-loop 5 and 6 |
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 Keywords |  RNA / SL5 / coronavirus / 5' UTR |
