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@ARTICLE{Wittlich:60123,
author = {Wittlich, M. and Wiesehan, K. and Koenig, B. W. and
Willbold, D.},
title = {{E}xpression, purification and membrane reconstitution of a
{CD}4 fragment comprising the transmembrane and cyctoplasmic
domains of the receptor},
journal = {Protein expression and purification},
volume = {55},
issn = {1046-5928},
address = {Orlando, Fla.},
publisher = {Academic Press},
reportid = {PreJuSER-60123},
pages = {198 - 207},
year = {2007},
note = {Record converted from VDB: 12.11.2012},
abstract = {The transmembrane glycoprotein CD4 plays a prominent role
in the adaptive immune response. CD4 is displayed primarily
on the surface of T helper cells, but also on subsets of
memory and regulatory T lymphocytes, macrophages, and
dendritic cells. Binding of the lymphocyte specific tyrosine
kinase p56(lck) to the cytoplasmic domain of CD4 is crucial
for antigen receptor-mediated signal transduction. The human
immunodeficiency virus (HIV) utilizes CD4 as the main
receptor for T cell invasion. The virus has developed
multiple strategies for down-regulation of CD4 in infected
cells. Physical interactions of viral proteins VpU and Nef
with the cytoplasmic tail of CD4 initiate a cascade of
events leading to degradation of CD4. Here we report
heterologous expression and purification of a CD4 fragment
comprising the transmembrane and cytoplasmic domains of
human CD4. A synthetic gene encoding CD4 amino acid residues
372-433 and a protease cleavage site was cloned into the
pTKK19xb/ub plasmid. The CD4 fragment was expressed in
Escherichia coli C43(DE3) cells as a ubiquitin fusion with
an N-terminal His-tag, isolated, released by PreScission
proteolytic cleavage, and purified to homogeneity.
Incorporation of the recombinant CD4 fragment in lipid
membranes and physical interaction with the cytoplasmic
domain of VpU was demonstrated by centrifugation assays
followed by reversed phase chromatographic analysis of the
composition of the proteoliposomes. A high resolution NMR
spectrum of uniformly (15)N-labeled CD4 peptide in membrane
simulating micelles proves the possibility of solution NMR
studies of this CD4 fragment and of its molecular
complexes.},
keywords = {Amino Acid Sequence / Antigens, CD4: biosynthesis /
Antigens, CD4: genetics / Antigens, CD4: isolation $\&$
purification / Cell Membrane: chemistry / Escherichia coli:
genetics / Genes, Synthetic / Humans / Liposomes: chemistry
/ Molecular Sequence Data / Nuclear Magnetic Resonance,
Biomolecular / Protein Structure, Tertiary / Recombinant
Proteins: biosynthesis / Recombinant Proteins: chemistry /
Recombinant Proteins: isolation $\&$ purification / Viral
Regulatory and Accessory Proteins: chemistry / Antigens, CD4
(NLM Chemicals) / Liposomes (NLM Chemicals) / Recombinant
Proteins (NLM Chemicals) / Viral Regulatory and Accessory
Proteins (NLM Chemicals) / J (WoSType)},
cin = {INB-2 / JARA-SIM},
ddc = {570},
cid = {I:(DE-Juel1)VDB805 / I:(DE-Juel1)VDB1045},
pnm = {Funktion und Dysfunktion des Nervensystems},
pid = {G:(DE-Juel1)FUEK409},
shelfmark = {Biochemical Research Methods / Biochemistry $\&$ Molecular
Biology / Biotechnology $\&$ Applied Microbiology},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:17613246},
UT = {WOS:000249631800023},
doi = {10.1016/j.pep.2007.05.007},
url = {https://juser.fz-juelich.de/record/60123},
}