Journal
STRUCTURE
Volume 28, Issue 9, Pages 979-+Publisher
CELL PRESS
DOI: 10.1016/j.str.2020.07.001
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Funding
- United States Department of Energy, Office of Science, Office of Basic Energy Sciences [W-31-109-Eng-38]
- NIGMS [R01GM130950]
- Emory University School of Medicine
- College of Liberal Arts and Sciences at the University of Kansas
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The M2-1 protein of human respiratory syncytial virus (HRSV) is a transcription anti-terminator that regulates the processivity of the HRSV RNA-dependent RNA polymerase (RdRP). Here, we report a crystal structure of HRSV M2-1 bound to a short positive-sense gene-end RNA (SH7) at 2.7 angstrom resolution. We identified multiple critical residues of M2-1 involved in RNA interaction and examined their roles using mutagenesis and Micro-Scale Thermophoresis (MST) assay. We found that hydrophobic residue Phe23 is indispensable for M2-1 to recognize the base of RNA. We also captured spontaneous binding of RNA (SH7) to M2-1 in all-atom simulations using a robust Gaussian accelerated molecular dynamics (GaMD) method. Both experiments and simulations revealed that the interactions of RNA with two separate domains of M2-1, the zinc-binding domain (ZBD) and the core domain (CD), are independent of each other. Collectively, our results provided a structural basis for RNA recognition by HRSV M2-1.
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