Project B01

Herpes simplex virus-1 (HSV-1) virions are covered with hundreds of glycoproteins of more than 12 different kinds¹. The fusion machinery of HSV-1, responsible for mediating fusion of the viral membrane with the plasma or endosomal membrane, consists of four essential glycoproteins, including glycoprotein B (gB) which is the bona fide fusion protein. During the fusion process gB changes its conformation from a pre-fusion to a post-fusion state. While the post-fusion conformation is highly stable and has been structurally resolved already in 2006 using X-ray crystallography, the pre-fusion conformation of gB eluded scientist for a long time due to its metastability, which is inherent to many pre-fusion forms of other viral fusion proteins as well. Recently, the pre-fusion conformation was solved using sub-volume averaging from cryo-electron tomography (cryo-ET) data after insertion of a stabilizing mutation². The pre-fusion conformation of viral fusion proteins can be an important target for prevention and treatment of viral infections. Furthermore, solving the pre-fusion structure was the first step in understanding the fusion mechanism in more detail.