Journal Article

PreJuSER-22825

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Mapping the interaction between the cytoplasmic domains of HIV-1 VpU and human CD4 using NMR spectroscopy.

Singh, S.FZJ* ; Möckel, L.FZJ* ; Thiagarajan-Rosenkranz, P.FZJ* ; Wittlich, M.FZJ* ; Willbold, D.FZJ* ; Koenig, B.FZJ*

2012
Wiley-Blackwell Oxford [u.a.]

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Please use a persistent id in citations: doi:10.1111/j.1742-4658.2012.08732.x

Abstract: Viral protein U (VpU) of HIV-1 plays an important role in downregulation of the main HIV-1 receptor CD4 from the surface of infected cells. Physical binding of VpU to newly synthesized CD4 in the endoplasmic reticulum is an early step in a pathway leading to proteasomal degradation of CD4. In this study, regions in the cytoplasmic domain of VpU involved in CD4 binding were identified by NMR spectroscopy. Amino acids in both helices found in the cytoplasmic region of VpU in membrane-mimicking detergent micelles experience chemical shift perturbations upon binding to CD4, whereas amino acids between the two helices and at the C-terminus of VpU show no or only small changes, respectively. The topology of the complex was further studied with paramagnetic relaxation enhancement. Paramagnetic spin labels were attached at three sequence positions of a CD4 peptide comprising the transmembrane and cytosolic domains of the receptor. VpU binds to a membrane-proximal region in the cytoplasmic domain of CD4.

Keyword(s): J ; CD4 (auto) ; HIV-1 (auto) ; NMR (auto) ; protein interaction (auto) ; viral protein U (auto)

Note: S. K. Singh is a collegiate of the Jurgen Manchot graduate school 'Molecules of infection' at the Heinrich Heine University Dusseldorf. This work was supported by a grant from the Prasidentenfond der Helmholtz-Gemeinschaft (HGF, 'Virtual Institute of Structural Biology') to D. Willbold.

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Contributing Institute(s):

1. Strukturbiochemie (ICS-6)

Research Program(s):

1. Funktion und Dysfunktion des Nervensystems (P33)
2. BioSoft: Makromolekulare Systeme und biologische Informationsverarbeitung (P45)

Appears in the scientific report 2012

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Database coverage:
; BIOSIS Previews ; Current Contents - Life Sciences ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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