Structure of the active domain of the herpes simplex virus protein ICP47 in water/sodium dodecyl sulfate solution determined by nuclear magnetic resonance spectroscopy

ICP47 encoded by herpes simplex virus (HSV) is a key factor in the evasion of cellular immune response against HSV-infected cells. By specific inhibit ion of the transporter associated with antigen processing (TAP), ICP47 prev ents peptide transport into the endoplasmic reticulum and subsequent loadin g of major histocompatibility complex (MHC) class I molecules. Amino acid r esidues 3-34 have been identified as the active domain. This domain appeare d to be unstructured in aqueous solution, whereas after binding to membrane s an alpha-helical conformation was observed. Here, we have analyzed the st ructure of ICP47(2-34) in a lipidlike environment by nuclear magnetic reson ance (NMR) spectroscopy. In micellar solution of deuterated sodium dodecyl sulfate, the viral TAP inhibitor adopts an ordered structure. There are two helical regions extending from residues 4 to 15 and from residues 22 to 32 . Arg-16 is found on the C-terminus of the first helix, and Gly-33 serves a s a terminator of the second helix. A loop between residues 17 and 21 is al so evident in the structure. The relative orientation of the helices toward each other, however, could not be determined due to the paucity of NOEs fr om residues 18-21.