| Structural highlights
Function
ICP47_HHV11 Plays a role in the inhibition of host immune response. Binds specifically to transporters associated with antigen processing (TAP), thereby blocking peptide-binding and translocation by TAP as well as subsequent loading of peptides onto MHC class I molecules. Empty MHC I molecules are retained in the endoplasmic reticulum and ultimately directed to proteasomal degradation. In consequence, infected cells are masked for immune recognition by cytotoxic T-lymphocytes.[1] [2] [3] [4]
Publication Abstract from PubMed
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.
Structure of the active domain of the herpes simplex virus protein ICP47 in water/sodium dodecyl sulfate solution determined by nuclear magnetic resonance spectroscopy.,Pfander R, Neumann L, Zweckstetter M, Seger C, Holak TA, Tampe R Biochemistry. 1999 Oct 12;38(41):13692-8. PMID:10521276[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Easterfield AJ, Austen BM, Westwood OM. Inhibition of antigen transport by expression of infected cell peptide 47 (ICP47) prevents cell surface expression of HLA in choriocarcinoma cell lines. J Reprod Immunol. 2001 Apr;50(1):19-40. PMID:11254939
- ↑ Fruh K, Ahn K, Djaballah H, Sempe P, van Endert PM, Tampe R, Peterson PA, Yang Y. A viral inhibitor of peptide transporters for antigen presentation. Nature. 1995 Jun 1;375(6530):415-8. PMID:7760936 doi:http://dx.doi.org/10.1038/375415a0
- ↑ York IA, Roop C, Andrews DW, Riddell SR, Graham FL, Johnson DC. A cytosolic herpes simplex virus protein inhibits antigen presentation to CD8+ T lymphocytes. Cell. 1994 May 20;77(4):525-35. PMID:8187174
- ↑ Ahn K, Meyer TH, Uebel S, Sempe P, Djaballah H, Yang Y, Peterson PA, Fruh K, Tampe R. Molecular mechanism and species specificity of TAP inhibition by herpes simplex virus ICP47. EMBO J. 1996 Jul 1;15(13):3247-55. PMID:8670825
- ↑ Pfander R, Neumann L, Zweckstetter M, Seger C, Holak TA, Tampe R. Structure of the active domain of the herpes simplex virus protein ICP47 in water/sodium dodecyl sulfate solution determined by nuclear magnetic resonance spectroscopy. Biochemistry. 1999 Oct 12;38(41):13692-8. PMID:10521276
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