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6pzq

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

Structural highlights

6pzq is a 6 chain structure with sequence from Human respiratory syncytial virus A2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.703Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

M21_HRSVA Acts as a transcriptional elongation factor to prevent premature termination during transcription thus allowing complete synthesis of RSV mRNAs. Functions also as a processivity and antitermination factor to permit transit of the polymerase through intergenic regions to access promoter distal genes. Plays a role in the association of the matrix protein with the nucleocapsid, which initiates assembly and budding. Also, can activate NF-kappa-B through association with host RELA.^[1] ^[2] ^[3]

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.

References

↑ Collins PL, Hill MG, Cristina J, Grosfeld H. Transcription elongation factor of respiratory syncytial virus, a nonsegmented negative-strand RNA virus. Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):81-5. PMID:8552680
↑ Hardy RW, Wertz GW. The product of the respiratory syncytial virus M2 gene ORF1 enhances readthrough of intergenic junctions during viral transcription. J Virol. 1998 Jan;72(1):520-6. PMID:9420254
↑ Fearns R, Collins PL. Role of the M2-1 transcription antitermination protein of respiratory syncytial virus in sequential transcription. J Virol. 1999 Jul;73(7):5852-64. PMID:10364337
↑ 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 of the Human Respiratory Syncytial Virus M2-1 Protein in Complex with a Short Positive-Sense Gene-End RNA. Structure. 2020 Sep 1;28(9):979-990.e4. PMID:32697936 doi:10.1016/j.str.2020.07.001