8UYE

BtCoV-HKU5 5' proximal stem-loop 5, conformation 1

Summary for 8UYE

• Entry DOI: 10.2210/pdb8uye/pdb
• EMDB information: 42801
• Descriptor: BtCoV-HKU5 5' proximal stem-loop 5 (1 entity in total)
• Functional Keywords: sl5, coronavirus, 5' utr, rna
• Biological source: Pipistrellus bat coronavirus HKU5
• Total number of polymer chains: 1
• Total formula weight: 43510.68

Authors

Kretsch, R.C.,Xu, L.,Zheludev, I.N.,Zhou, X.,Huang, R.,Nye, G.,Li, S.,Zhang, K.,Chiu, W.,Das, R. (deposition date: 2023-11-13, release date: 2023-12-06, Last modification date: 2024-03-13)

Primary citation

Kretsch, R.C.,Xu, L.,Zheludev, I.N.,Zhou, X.,Huang, R.,Nye, G.,Li, S.,Zhang, K.,Chiu, W.,Das, R.
Tertiary folds of the SL5 RNA from the 5' proximal region of SARS-CoV-2 and related coronaviruses.
Proc.Natl.Acad.Sci.USA, 121:e2320493121-e2320493121, 2024

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 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.

PubMed: 38427602
DOI: 10.1073/pnas.2320493121

Experimental method

ELECTRON MICROSCOPY (5.9 Å)