4NZ0

The EMCV 3Dpol structure at 2.8A resolution

Summary for 4NZ0

• Entry DOI: 10.2210/pdb4nz0/pdb
• Related: 1U09 4nyz
• Descriptor: Genome polyprotein, GLYCEROL, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: encephalomyocarditis virus, close right hand, rna dependent rna polymerase, transferase
• Biological source: Mengo virus
• Cellular location: Protein 2A: Host nucleus . Protein VP2: Virion. Protein VP3: Virion. Protein VP1: Virion. Protein 2B: Host cytoplasmic vesicle membrane ; Peripheral membrane protein ; Cytoplasmic side . Protein 2C: Host cytoplasmic vesicle membrane ; Peripheral membrane protein ; Cytoplasmic side . Protein 3A: Host cytoplasmic vesicle membrane ; Peripheral membrane protein ; Cytoplasmic side . Protein 3B: Virion . Protease 3C: Host cytoplasm . RNA-directed RNA polymerase 3D-POL: Host cytoplasmic vesicle membrane ; Peripheral membrane protein ; Cytoplasmic side : P12296
• Total number of polymer chains: 6
• Total formula weight: 314239.23

Authors

Vives-adrian, L.,Ferrer-orta, C.,Verdaguer, N. (deposition date: 2013-12-11, release date: 2014-03-19, Last modification date: 2024-11-06)

Primary citation

Vives-Adrian, L.,Lujan, C.,Oliva, B.,van der Linden, L.,Selisko, B.,Coutard, B.,Canard, B.,van Kuppeveld, F.J.,Ferrer-Orta, C.,Verdaguer, N.
The crystal structure of a cardiovirus RNA-dependent RNA polymerase reveals an unusual conformation of the polymerase active site
J.Virol., 88:5595-5607, 2014

PubMed Abstract: Encephalomyocarditis virus (EMCV) is a member of the Cardiovirus genus within the large Picornaviridae family, which includes a number of important human and animal pathogens. The RNA-dependent RNA polymerase (RdRp) 3Dpol is a key enzyme for viral genome replication. In this study, we report the X-ray structures of two different crystal forms of the EMCV RdRp determined at 2.8- and 2.15-Å resolution. The in vitro elongation and VPg uridylylation activities of the purified enzyme have also been demonstrated. Although the overall structure of EMCV 3Dpol is shown to be similar to that of the known RdRps of other members of the Picornaviridae family, structural comparisons show a large reorganization of the active-site cavity in one of the crystal forms. The rearrangement affects mainly motif A, where the conserved residue Asp240, involved in ribonucleoside triphosphate (rNTP) selection, and its neighbor residue, Phe239, move about 10 Å from their expected positions within the ribose binding pocket toward the entrance of the rNTP tunnel. This altered conformation of motif A is stabilized by a cation-π interaction established between the aromatic ring of Phe239 and the side chain of Lys56 within the finger domain. Other contacts, involving Phe239 and different residues of motif F, are also observed. The movement of motif A is connected with important conformational changes in the finger region flanked by residues 54 to 63, harboring Lys56, and in the polymerase N terminus. The structures determined in this work provide essential information for studies on the cardiovirus RNA replication process and may have important implications for the development of new antivirals targeting the altered conformation of motif A.

PubMed: 24600002
DOI: 10.1128/JVI.03502-13

Experimental method

X-RAY DIFFRACTION (2.8 Å)