1RAJ

Poliovirus Polymerase with a 68 residue N-terminal truncation

Summary for 1RAJ

• Entry DOI: 10.2210/pdb1raj/pdb
• Related: 1RA6 1RA7 1RDR 1TQL
• Descriptor: Genome polyprotein (2 entities in total)
• Functional Keywords: nucleotidyltransferase, poliovirus, polio, 3d, rna-dependent, polymerase, transferase
• Biological source: Human poliovirus 1
• Cellular location: Capsid protein VP0: Virion. Capsid protein VP4: Virion. Capsid protein VP2: Virion. Capsid protein VP3: Virion. Capsid 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 3AB: Host cytoplasmic vesicle membrane ; Peripheral membrane protein ; Cytoplasmic side . Viral protein genome-linked: Virion. Protease 3C: Host cytoplasm. Protein 3CD: Host cytoplasmic vesicle membrane ; Peripheral membrane protein ; Cytoplasmic side . RNA-directed RNA polymerase: Host cytoplasmic vesicle membrane ; Peripheral membrane protein ; Cytoplasmic side : P03300
• Total number of polymer chains: 1
• Total formula weight: 44793.12

Authors

Thompson, A.A.,Peersen, O.B. (deposition date: 2003-10-31, release date: 2004-08-17, Last modification date: 2023-08-23)

Primary citation

Thompson, A.A.,Peersen, O.B.
Structural basis for proteolysis-dependent activation of the poliovirus RNA-dependent RNA polymerase.
Embo J., 23:3462-3471, 2004

PubMed Abstract: The active RNA-dependent RNA polymerase of poliovirus, 3Dpol, is generated by cleavage of the 3CDpro precursor protein, a protease that has no polymerase activity despite containing the entire polymerase domain. By intentionally disrupting a known and persistent crystal packing interaction, we have crystallized the poliovirus polymerase in a new space group and solved the complete structure of the protein at 2.0 A resolution. It shows that the N-terminus of fully processed 3Dpol is buried in a surface pocket where it makes hydrogen bonds that act to position Asp238 in the active site. Asp238 is an essential residue that selects for the 2' OH group of substrate rNTPs, as shown by a 2.35 A structure of a 3Dpol-GTP complex. Mutational, biochemical, and structural data further demonstrate that 3Dpol activity is exquisitely sensitive to mutations at the N-terminus. This sensitivity is the result of allosteric effects where the structure around the buried N-terminus directly affects the positioning of Asp238 in the active site.

PubMed: 15306852
DOI: 10.1038/sj.emboj.7600357

Experimental method

X-RAY DIFFRACTION (2.5 Å)