Conformational flexibility in the enterovirus RNA replication platform

• Published in: RNA (Cambridge) Vol. 25; no. 3; pp. 376 - 387
• Main Authors: Warden, Meghan S, Cai, Kai, Cornilescu, Gabriel, Burke, Jordan E, Ponniah, Komala, Butcher, Samuel E, Pascal, Steven M
• Format: Journal Article
• Language: English
• Published: United States Cold Spring Harbor Laboratory Press 01.03.2019
• Subjects: Enterovirus - genetics; Enteroviruses; Gene Expression Regulation, Viral; Genomes; Magnesium; Magnesium - chemistry; Magnetic Resonance Spectroscopy; Models, Molecular; NMR; Nuclear magnetic resonance; Nucleic Acid Conformation; Protein interaction; Protein structure; Replication initiation; Rhinovirus; Ribonucleic acid; RNA; RNA, Viral - chemistry; RNA, Viral - genetics; Structure-Activity Relationship; Transcription, Genetic; Virus Replication; X-ray scattering; replication; NMR; cloverleaf; RNA; enterovirus; SAXS
• ISSN: 1355-8382; 1469-9001
• DOI: 10.1261/rna.069476.118

A presumed RNA cloverleaf (5'CL), located at the 5'-most end of the noncoding region of the enterovirus genome, is the primary established site for initiation of genomic replication. Stem-loop B (SLB) and stem-loop D (SLD), the two largest stem-loops within the 5'CL, serve as recognition sites for protein interactions that are essential for replication. Here we present the solution structure of rhinovirus serotype 14 5'CL using a combination of nuclear magnetic resonance spectroscopy and small-angle X-ray scattering. In the of magnesium, the structure adopts an open, somewhat extended conformation. In the of magnesium, the structure compacts, bringing SLB and SLD into close contact, a geometry that creates an extensive accessible major groove surface, and permits interaction between the proteins that target each stem-loop.