Journal Article

PreJuSER-6550

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png NMR structural characterization of HIV-1 virus protein U cytoplasmic domain in the presence of dodecylphosphatidylcholine micelles

Wittlich, M.FZJ* ; Koenig, B. W.FZJ* ; Stoldt, M.FZJ* ; Schmidt, H. ; Willbold, D.FZJ*

2009
Wiley-Blackwell Oxford [u.a.]

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Please use a persistent id in citations: doi:10.1111/j.1742-4658.2009.07363.x

Abstract: The HIV-1 encoded virus protein U (VpU) is required for efficient viral release from human host cells and for induction of CD4 degradation in the endoplasmic reticulum. The cytoplasmic domain of the membrane protein VpU (VpUcyt) is essential for the latter activity. The structure and dynamics of VpUcyt were characterized in the presence of membrane simulating dodecylphosphatidylcholine (DPC) micelles by high-resolution liquid state NMR. VpUcyt is unstructured in aqueous buffer. The addition of DPC micelles induces a well-defined membrane proximal alpha-helix (residues I39-E48) and an additional helical segment (residues L64-R70). A tight loop (L73-V78) is observed close to the C-terminus, whereas the interhelical linker (R49-E63) remains highly flexible. A 3D structure of VpUcyt in the presence of DPC micelles was calculated from a large set of proton-proton distance constraints. The topology of micelle-associated VpUcyt was derived from paramagnetic relaxation enhancement of protein nuclear spins after the introduction of paramagnetic probes into the interior of the micelle or the aqueous buffer. Qualitative analysis of secondary chemical shift and paramagnetic relaxation enhancement data in conjunction with dynamic information from heteronuclear NOEs and structural insight from homonuclear NOE-based distance constraints indicated that micelle-associated VpUcyt retains a substantial degree of structural flexibility.

Keyword(s): HIV-1: chemistry (MeSH) ; HIV-1: metabolism (MeSH) ; Human Immunodeficiency Virus Proteins: chemistry (MeSH) ; Magnetic Resonance Spectroscopy (MeSH) ; Micelles (MeSH) ; Phosphorylcholine: analogs & derivatives (MeSH) ; Phosphorylcholine: chemistry (MeSH) ; Protein Structure, Tertiary (MeSH) ; Viral Regulatory and Accessory Proteins: chemistry (MeSH) ; Human Immunodeficiency Virus Proteins ; Micelles ; Viral Regulatory and Accessory Proteins ; vpu protein, Human immunodeficiency virus 1 ; Phosphorylcholine ; dodecylphosphocholine ; J ; CD4 (auto) ; DPC micelle (auto) ; HIV-1 VpU (auto) ; NMR (auto) ; solution structure (auto)

Note: This work was supported by a grant from the Prasidentenfond der Helmholtzgemeinschaft (HGF, Virtual Institute of Structural Biology) to DW.

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Contributing Institute(s):

1. Strukturbiochemie (ISB-3)

Research Program(s):

1. Funktion und Dysfunktion des Nervensystems (P33)

Appears in the scientific report 2009

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