6PZQ

Structure of the human respiratory syncytial virus M2-1 protein in complex with a short positive-sense gene-end RNA

Summary for 6PZQ

• Entry DOI: 10.2210/pdb6pzq/pdb
• Descriptor: Matrix M2-1, RNA (5'-R(P*GP*UP*UP*AP*AP*U)-3'), ZINC ION, ... (4 entities in total)
• Functional Keywords: hrsv m2-1 rna complex, rna binding protein, metal binding protein-rna complex, metal binding protein/rna
• Biological source: Human respiratory syncytial virus A (strain A2); More
• Total number of polymer chains: 6
• Total formula weight: 93539.98

Authors

Gao, Y.,Cao, D.,Liang, B. (deposition date: 2019-08-01, release date: 2020-08-05, Last modification date: 2024-11-13)

Primary citation

Gao, Y.,Cao, D.,Pawnikar, S.,John, K.P.,Ahn, H.M.,Hill, S.,Ha, J.M.,Parikh, P.,Ogilvie, C.,Swain, A.,Yang, A.,Bell, A.,Salazar, A.,Miao, Y.,Liang, B.
Structure of the Human Respiratory Syncytial Virus M2-1 Protein in Complex with a Short Positive-Sense Gene-End RNA.
Structure, 28:979-, 2020

PubMed Abstract: 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 Å 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.

PubMed: 32697936
DOI: 10.1016/j.str.2020.07.001

Experimental method

X-RAY DIFFRACTION (2.703 Å)