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Title: Crystal structure of a highly conserved enteroviral 5′ cloverleaf RNA replication element
The extreme 5′-end of the enterovirus RNA genome contains a conserved cloverleaf-like domain that recruits 3CD and PCBP proteins required for initiating genome replication. Here, we report the crystal structure at 1.9 Å resolution of this domain from the CVB3 genome in complex with an antibody chaperone. The RNA folds into an antiparallel H-type four-way junction comprising four subdomains with co-axially stacked sA-sD and sB-sC helices. Long-range interactions between a conserved A40 in the sC-loop and Py-Py helix within the sD subdomain organize near-parallel orientations of the sA-sB and sC-sD helices. Our NMR studies confirm that these long-range interactions occur in solution and without the chaperone. The phylogenetic analyses indicate that our crystal structure represents a conserved architecture of enteroviral cloverleaf-like domains, including the A40 and Py-Py interactions. The protein binding studies further suggest that the H-shape architecture provides a ready-made platform to recruit 3CD and PCBP2 for viral replication.  more » « less
Award ID(s):
2236996
PAR ID:
10478255
Author(s) / Creator(s):
; ; ; ; ; ;
Publisher / Repository:
Nature Portfolio
Date Published:
Journal Name:
Nature communications
ISSN:
2041-1723
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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