High-resolution structure of the cofactor regenerator formate dehydrogenase from candida boidinii

Vesicular Stomatitis virus glycoprotein (VSV-G) is involved in both receptor recognition and membrane fusion. Fusion is triggered by low pH-induced structural rearrangements and G can assume at least three different conformations: The native state detected at the viral surface above pH 7, the activated hydrophobic state which interacts with the target membrane as a first step of the fusion process, and the fusion-inactive conformation. There is a pH dependent equilibrium between the different states of G that is shifted toward the inactive state at low pH. Thus, differently from fusogenic glycoproteins from other viral families, the low-pH induced conformational change is reversible. Using limited proteolysis, we have obtained and crystallised a soluble ectodomain of VSV-G in both its neutral and low pH conformations. The structures show that VSV-G is not homologous to any other fusion protein of known structure. Strikingly, VSV-G shares features of both class I and class II fusion proteins, indicative of convergent evolution. The structures also show the extent of the conformational rearrangements and the molecular basis of reversibility. These results invite us to reconsider many questions on the evolution of viruses. m07b.o03