Pfänder R, Neumann L, Zweckstetter M, Seger C, Holak T A, Tampé R
Max-Planck-Institut für Biochemie, Martinsried, Germany.
Biochemistry. 1999 Oct 12;38(41):13692-8. doi: 10.1021/bi9909647.
ICP47 encoded by herpes simplex virus (HSV) is a key factor in the evasion of cellular immune response against HSV-infected cells. By specific inhibition of the transporter associated with antigen processing (TAP), ICP47 prevents peptide transport into the endoplasmic reticulum and subsequent loading of major histocompatibility complex (MHC) class I molecules. Amino acid residues 3-34 have been identified as the active domain. This domain appeared to be unstructured in aqueous solution, whereas after binding to membranes an alpha-helical conformation was observed. Here, we have analyzed the structure of ICP47(2-34) in a lipidlike environment by nuclear magnetic resonance (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 as a terminator of the second helix. A loop between residues 17 and 21 is also evident in the structure. The relative orientation of the helices toward each other, however, could not be determined due to the paucity of NOEs from residues 18-21.
单纯疱疹病毒（HSV）编码的ICP47是逃避针对HSV感染细胞的细胞免疫反应的关键因素。通过特异性抑制与抗原加工相关的转运体（TAP），ICP47可阻止肽转运至内质网以及随后主要组织相容性复合体（MHC）I类分子的负载。氨基酸残基3 - 34已被确定为活性结构域。该结构域在水溶液中似乎是无序的，而在与膜结合后观察到α - 螺旋构象。在此，我们通过核磁共振（NMR）光谱分析了脂质样环境中ICP47(2 - 34)的结构。在氘代十二烷基硫酸钠的胶束溶液中，病毒TAP抑制剂呈现出有序结构。有两个螺旋区域，分别从残基4延伸至15以及从残基22延伸至32。精氨酸 - 16位于第一个螺旋的C末端，甘氨酸 - 33作为第二个螺旋的终止子。在该结构中，残基17和21之间的环也很明显。然而，由于残基18 - 21的核Overhauser效应（NOE）较少，无法确定螺旋之间的相对取向。
