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@ARTICLE{Wittlich:7147,
author = {Wittlich, M. and Thiagarajan, P. and Koenig, B. W. and
Hartmann, R. and Willbold, D.},
title = {{NMR} structure of the transmembrane and cytoplasmic
domains of human {CD}4 in micelles},
journal = {Biochimica et biophysica acta},
volume = {1798},
issn = {0006-3002},
address = {Amsterdam [u.a.]},
publisher = {Elsevier},
reportid = {PreJuSER-7147},
pages = {122 - 127},
year = {2010},
note = {This work has been supported by a grant from the
"Prasidentenfond der Helmholtzgemeinschaft" (HGF, "Virtual
Institute of Structural Biology") to D.W.},
abstract = {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.},
keywords = {Antigens, CD4: chemistry / Antigens, CD4: immunology /
Antigens, CD4: metabolism / Humans / Micelles / Nuclear
Magnetic Resonance, Biomolecular: methods /
Phosphorylcholine: analogs $\&$ derivatives /
Phosphorylcholine: chemistry / Phosphorylcholine: metabolism
/ Protein Structure, Secondary: physiology / Protein
Structure, Tertiary: physiology / Antigens, CD4 (NLM
Chemicals) / Micelles (NLM Chemicals) / Phosphorylcholine
(NLM Chemicals) / dodecylphosphocholine (NLM Chemicals) / J
(WoSType)},
cin = {ISB-3 / JARA-HPC},
ddc = {570},
cid = {I:(DE-Juel1)VDB942 / $I:(DE-82)080012_20140620$},
pnm = {Funktion und Dysfunktion des Nervensystems / BioSoft:
Makromolekulare Systeme und biologische
Informationsverarbeitung},
pid = {G:(DE-Juel1)FUEK409 / G:(DE-Juel1)FUEK505},
shelfmark = {Biochemistry $\&$ Molecular Biology / Biophysics},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:19781520},
UT = {WOS:000274859300009},
doi = {10.1016/j.bbamem.2009.09.010},
url = {https://juser.fz-juelich.de/record/7147},
}