TY  - JOUR
AU  - Wittlich, M.
AU  - Thiagarajan, P.
AU  - Koenig, B. W.
AU  - Hartmann, R.
AU  - Willbold, D.
TI  - NMR structure of the transmembrane and cytoplasmic domains of human CD4 in micelles
JO  - Biochimica et biophysica acta
VL  - 1798
SN  - 0006-3002
CY  - Amsterdam [u.a.]
PB  - Elsevier
M1  - PreJuSER-7147
SP  - 122 - 127
PY  - 2010
N1  - This work has been supported by a grant from the "Prasidentenfond der Helmholtzgemeinschaft" (HGF, "Virtual Institute of Structural Biology") to D.W.
AB  - The human cluster determinant 4 (CD4) is a type I transmembrane glycoprotein involved in T-cell signalling. It is expressed primarily on the surface of T helper cells but also on subsets of memory and regulatory T lymphocytes (CD4(+) cells). It serves as a coreceptor in T-cell receptor recognition of MHC II antigen complexes. Besides its cellular functions, CD4 serves as the main receptor for human immunodeficiency virus type I (HIV-1). During T-cell infection, the CD4 extracellular domain is bound by HIV-1 gp120, the viral surface glycoprotein, which triggers a number of conformational changes ultimately resulting in virion entry of the cell. Subsequently, CD4 is downregulated in infected cells by multiple strategies that involve direct interactions of the HIV-1 proteins VpU and Nef with the cytoplasmic part of CD4. In the present work, we describe the NOE-based solution structure of the transmembrane and cytoplasmic domains of the cystein-free variant of CD4 (CD4mut) in dodecylphosphocholine (DPC) micelles. Furthermore, we have characterized micelle-inserted CD4mut by paramagentic relaxation enhancement (PRE) agents and (1)H-(15)N heteronuclear NOE data. CD4mut features a stable and well-defined transmembrane helix from M372 to V395 buried in the micellar core and a cytoplasmic helix ranging from A404 to L413. Experimental data suggest the amphipathic cytoplasmic helix to be in close contact with the micellar surface. The role of the amphipathic helix and its interaction with the micellar surface is discussed with respect to the biological function of the full-length CD4 protein.
KW  - Antigens, CD4: chemistry
KW  - Antigens, CD4: immunology
KW  - Antigens, CD4: metabolism
KW  - Humans
KW  - Micelles
KW  - Nuclear Magnetic Resonance, Biomolecular: methods
KW  - Phosphorylcholine: analogs & derivatives
KW  - Phosphorylcholine: chemistry
KW  - Phosphorylcholine: metabolism
KW  - Protein Structure, Secondary: physiology
KW  - Protein Structure, Tertiary: physiology
KW  - Antigens, CD4 (NLM Chemicals)
KW  - Micelles (NLM Chemicals)
KW  - Phosphorylcholine (NLM Chemicals)
KW  - dodecylphosphocholine (NLM Chemicals)
KW  - J (WoSType)
LB  - PUB:(DE-HGF)16
C6  - pmid:19781520
UR  - <Go to ISI:>//WOS:000274859300009
DO  - DOI:10.1016/j.bbamem.2009.09.010
UR  - https://juser.fz-juelich.de/record/7147
ER  -