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Publication Abstract from PubMed

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 A resolution. We identified multiple critical residues of M2-1 involved in RNA interaction and examined their roles using mutagenesis and MicroScale 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.

Structure of the Human Respiratory Syncytial Virus M2-1 Protein in Complex with a Short Positive-Sense Gene-End RNA.,Gao Y, Cao D, Pawnikar S, John KP, Ahn HM, Hill S, Ha JM, Parikh P, Ogilvie C, Swain A, Yang A, Bell A, Salazar A, Miao Y, Liang B Structure. 2020 Sep 1;28(9):979-990.e4. doi: 10.1016/j.str.2020.07.001. Epub 2020, Jul 21. PMID:32697936^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.