TY  - JOUR
A1  - Aisenbrey, Christopher
A1  - Sizun, Christina
A1  - Koch, Joachim
A1  - Herget, Meike
A1  - Abele, Rupert
A1  - Bechinger, Burkhard
A1  - Tampé, Robert
T1  - Structure and dynamics of membrane-associated ICP47, a viral inhibitor of the MHC I antigen-processing machinery
T2  - Journal of biological chemistry
N2  - To evade the host's immune response, herpes simplex virus employs the immediate early gene product ICP47 (IE12) to suppress antigen presentation to cytotoxic T-lymphocytes by inhibition of the ATP-binding cassette transporter associated with antigen processing (TAP). ICP47 is a membrane-associated protein adopting an alpha-helical conformation. Its active domain was mapped to residues 3-34 and shown to encode all functional properties of the full-length protein. The active domain of ICP47 was reconstituted into oriented phospholipid bilayers and studied by proton-decoupled 15N and 2H solid-state NMR spectroscopy. In phospholipid bilayers, the protein adopts a helix-loop-helix structure, where the average tilt angle of the helices relative to the membrane surface is approximately 15 degrees (+/- 7 degrees ). The alignment of both structured domains exhibits a mosaic spread of approximately 10 degrees . A flexible dynamic loop encompassing residues 17 and 18 separates the two helices. Refinement of the experimental data indicates that helix 1 inserts more deeply into the membrane. These novel insights into the structure of ICP47 represent an important step toward a molecular understanding of the immune evasion mechanism of herpes simplex virus and are instrumental for the design of new therapeutics.
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/76258
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-762581
SN  - 0021-9258
VL  - 281.2006
IS  - 41
SP  - 30365
EP  - 30372
PB  - American Society for Biochemistry and Molecular Biology Publications
CY  - Bethesda, Md
ER  -