The three HveA receptor ligands, gD, LT-alpha and LIGHT bind to distinct sites on HveA

The herpes virus entry mediator A (HveA), a member of the tumor necrosis fa ctor receptor (TNFR) superfamily, interacts with three different protein li gands; lymphotoxin-alpha (LT-alpha) and LIGHT (LIGHT stands for lymphotoxin homolog, which exhibits inducible expression and competes with HSV glycopr otein D for HveA and is expressed on T-lymphocytes) from the host and the h erpes simplex virus (HSV) surface glycoprotein go. It has been reported tha t the go binding site on HveA is located within the receptor's two N-termin al CRP domains, and that go and LIGHT compete for their binding to HveA. Ho wever, whether these ligands interact with the same or different sites on t he receptor is unclear. We analyzed and compared the sites of interaction b etween HveA and its TNF ligands, by using two recombinant forms of the rece ptor, comprising the full-receptor ectodomain (HveA (200t)) and its two fir st CRP domains (HveA (120t)), as well as several monoclonal antibodies reco gnizing HveA. Two HveA peptide ligands (BP-I and BP-2) that differentially inhibit binding of soluble go and LT-alpha to the receptor were also used t o demonstrate that go, LIGHT and LT-alpha bind to distinct sites on the rec eptor. Our results suggest that binding of a ligand to HveA may alter the c onformation of this receptor, thereby affecting its interaction with its ot her ligands. (C) 2001 Published by Elsevier Science Ltd.