Karposi’s Sacoma-Associated Herpes Virus (KSHV) is a member of the herpes virus family, and while KSHV is less ubiquitous than other herpes viruses within populations it is associated with cancer development, particularly in immunocompromised individuals 1,2.
KSHV is a DNA virus capable of modulating host immune responses via mimicry of endogenous Bcl-2 proteins, a protein family responsible for control of host-cell intrinsic apoptosis, a form of programmed cell death (PCD). The viral Bcl-2 (vBcl-2) expressed by KSHV, KSBcl-2, retains a minimal level of sequence homology with human Bcl-2, yet still maintains the necessary structure and function that allows for binding to pro-apoptotic proteins of the host, namely the BH3-only apoptosis sensitizers 3.
The BH3-only protein, Beclin 1, plays an important role in autophagy, a cellular response to stress enabling recycling of cellular constituents as a pro-survival strategy. It also acts as a mediator between the autophagy and apoptosis pathways and dysregulation of Beclin 1 is observed in many types of cancers. The BH3 motif of Beclin 1, which allows for its regulation by Bcl-2 proteins, thus makes it a logical target for vBcl-2’s, which can be observed with the direct binding interaction of KSBcl-2 with Beclin 1 3,4.
The far-reaching effects of this singular vBcl-2 makes it an attractive target for the development of therapeutics; therefore, this work aims to provide structural and mechanistic insights into the binding of KSBcl-2 to Beclin 1.