4u4i | pdb_00004u4i
Megavirus chilensis superoxide dismutase
Structural highlights
FunctionPublication Abstract from PubMedGiant viruses able to replicate in Acanthamoeba castellanii penetrate their host through phagocytosis. After capsid opening, a fusion between the internal membranes of the virion and the phagocytic vacuole triggers the transfer in the cytoplasm of the viral DNA together with the DNA repair enzymes and the transcription machinery present in the particles. In addition, the proteome analysis of Mimivirus purified virions revealed the presence of many enzymes meant to resist oxidative stress and conserved in the Mimiviridae. Megavirus chilensis encodes a predicted copper-zinc superoxide dismutase (SOD), an enzyme known to detoxify reactive oxygen species released in the course of host defense reactions. While it was thought that the metal ions were required for the formation of the active site lid and dimer stabilization, M. chilensis SOD forms a very stable metal-free dimer. We used EPR analysis and activity measurements to show that the supplementation of the bacterial culture with copper and zinc during the recombinant expression of Mg277 was sufficient to restore a fully active holo enzyme. These results demonstrate that the viral enzyme activation is independent of a chaperone both for disulfide bridge formation and copper incorporation, and suggest that its assembly may not be as regulated as that of its cellular counterparts. A SOD protein is encoded by a variety of DNA viruses but is absent from Mimivirus. As in Poxviruses, the enzyme might be dispensable when infecting Acanthamoeba cells but could allow M. chilensis to infect a broader range of eukaryotic hosts. IMPORTANCE: Mimiviridae are giant viruses encoding more than 1000 proteins. The virion particles are loaded with proteins used by the virus to resist the vacuole oxidative stress. Megavirus chilensis virion contain a predicted copper, zinc superoxide dismutase (Cu,Zn-SOD). The corresponding gene is present in some Megavirus chilensis relatives but is absent from Mimivirus. This first crystallographic structure of a viral Cu,Zn-SOD highlights the common features and differences of the viral enzyme compared to cellular SODs. It corresponds to a very stable dimer of the apo form of the enzyme. We demonstrate that upon growth medium supplementation of Cu and Zn the recombinant protein is fully active, suggesting that the viral SOD activation is independent on a copper chaperone for SOD generally used by eukaryotic SODs. The Megavirus chilensis Cu,Zn-Superoxide Dismutase: the first viral structure of a typical CCS-independent hyperstable dimeric enzyme.,Lartigue A, Burlat B, Coutard B, Chaspoul F, Claverie JM, Abergel C J Virol. 2014 Oct 29. pii: JVI.02588-14. PMID:25355875[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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