3GQE

Crystal structure of macro domain of Venezuelan Equine Encephalitis virus

Summary for 3GQE

• Entry DOI: 10.2210/pdb3gqe/pdb
• Related: 3GPG 3GPO 3GPQ
• Descriptor: Non-structural protein 3, BICINE (3 entities in total)
• Functional Keywords: macro domain, x domain, venezuelan equine encephalitis virus, alphavirus, virus, vizier. viral enzymes involved in replication, atp-binding, cell membrane, cell projection, endosome, helicase, hydrolase, lipoprotein, lysosome, membrane, methyltransferase, mrna capping, mrna processing, multifunctional enzyme, nucleotide-binding, nucleotidyltransferase, nucleus, palmitate, phosphoprotein, protease, rna replication, rna-binding, rna-directed rna polymerase, thiol protease, transferase, viral protein
• Biological source: Venezuelan equine encephalitis virus
• Cellular location: Non-structural polyprotein: Host endosome membrane; Peripheral membrane protein; Cytoplasmic side (By similarity). P123: Host endosome membrane; Peripheral membrane protein; Cytoplasmic side (By similarity). P123': Host endosome membrane; Peripheral membrane protein; Cytoplasmic side (By similarity). mRNA-capping enzyme nsP1: Host endosome membrane; Peripheral membrane protein; Cytoplasmic side (By similarity). Protease nsP2: Host endosome membrane; Peripheral membrane protein; Cytoplasmic side (By similarity). Non-structural protein 3: Host endosome membrane; Peripheral membrane protein; Cytoplasmic side (By similarity). Non-structural protein 3': Host endosome membrane; Peripheral membrane protein; Cytoplasmic side (By similarity). RNA-directed RNA polymerase nsP4: Host endosome membrane; Peripheral membrane protein; Cytoplasmic side (By similarity): P36328
• Total number of polymer chains: 2
• Total formula weight: 36892.91

Authors

Jamal, S.,Malet, H.,Coutard, B.,Canard, B. (deposition date: 2009-03-24, release date: 2009-07-21, Last modification date: 2024-11-06)

Primary citation

Malet, H.,Coutard, B.,Jamal, S.,Dutartre, H.,Papageorgiou, N.,Neuvonen, M.,Ahola, T.,Forrester, N.,Gould, E.A.,Lafitte, D.,Ferron, F.,Lescar, J.,Gorbalenya, A.E.,de Lamballerie, X.,Canard, B.
The crystal structures of Chikungunya and Venezuelan equine encephalitis virus nsP3 macro domains define a conserved adenosine binding pocket
J.Virol., 83:6534-6545, 2009

PubMed Abstract: Macro domains (also called "X domains") constitute a protein module family present in all kingdoms of life, including viruses of the Coronaviridae and Togaviridae families. Crystal structures of the macro domain from the Chikungunya virus (an "Old World" alphavirus) and the Venezuelan equine encephalitis virus (a "New World" alphavirus) were determined at resolutions of 1.65 and 2.30 A, respectively. These domains are active as adenosine di-phosphoribose 1''-phosphate phosphatases. Both the Chikungunya and the Venezuelan equine encephalitis virus macro domains are ADP-ribose binding modules, as revealed by structural and functional analysis. A single aspartic acid conserved through all macro domains is responsible for the specific binding of the adenine base. Sequence-unspecific binding to long, negatively charged polymers such as poly(ADP-ribose), DNA, and RNA is observed and attributed to positively charged patches outside of the active site pocket, as judged by mutagenesis and binding studies. The crystal structure of the Chikungunya virus macro domain with an RNA trimer shows a binding mode utilizing the same adenine-binding pocket as ADP-ribose, but avoiding the ADP-ribose 1''-phosphate phosphatase active site. This leaves the AMP binding site as the sole common feature in all macro domains.

PubMed: 19386706
DOI: 10.1128/JVI.00189-09

Experimental method

X-RAY DIFFRACTION (2.3 Å)