Evidence for [2Fe-2S]2+ and Linear [3Fe-4S]1+ Clusters in a Unique Family of Glycine/Cysteine-Rich Fe‑S Proteins from Megavirinae Giant Viruses

• Published in: Journal of the American Chemical Society 2023-02, Vol.145 (5), p.2733-2738
• Main Authors: Villalta, Alejandro, Srour, Batoul, Lartigue, Audrey, Clémancey, Martin, Byrne, Deborah, Chaspoul, Florence, Loquet, Antoine, Guigliarelli, Bruno, Blondin, Geneviève, Abergel, Chantal, Burlat, Bénédicte
• Format: Article
• Language: English
• Subjects: Cysteine - chemistry; Electron Spin Resonance Spectroscopy; Giant Viruses - metabolism; Glycine; Iron-Sulfur Proteins - chemistry; Life Sciences; Microbiology and Parasitology; Spectrum Analysis; Virology
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.2c10484

We have discovered a protein with an amino acid composition exceptionally rich in glycine and cysteine residues in the giant virus mimivirus. This small 6 kDa protein is among the most abundant proteins in the icosahedral 0.75 μm viral particles; it has no predicted function but is probably essential for infection. The aerobically purified red-brownish protein overproduced inEscherichia coli contained both iron and inorganic sulfide. UV/vis, EPR, and Mössbauer studies revealed that the viral protein, coined GciS, accommodated two distinct Fe-S clusters: a diamagnetic S = 0 [2Fe-2S]2+ cluster and a paramagnetic S = 5/2 linear [3Fe-4S]1+ cluster, a geometry rarely stabilized in native proteins. Orthologs of mimivirus GciS were identified within all clades of Megavirinae, a Mimiviridae subfamily infecting Acanthamoeba, including the distantly related tupanviruses, and displayed the same spectroscopic features. Thus, these glycine/cysteine-rich proteins form a new family of viral Fe-S proteins sharing unique Fe-S cluster binding properties.