TY  - JOUR
AU  - Wittlich, M.
AU  - Koenig, B. W.
AU  - Hoffmann, S.
AU  - Willbold, D.
TI  - Structural characterisation of the transmembrane and cytoplasmic domains of human CD4
JO  - Biochimica et biophysica acta / Biomembranes
VL  - 1768
SN  - 0005-2736
CY  - Amsterdam
PB  - Elsevier
M1  - PreJuSER-60128
SP  - 2949 - 2960
PY  - 2007
N1  - Record converted from VDB: 12.11.2012
AB  - Cluster determinant 4 (CD4) is a type I transmembrane glycoprotein of 58 kDa. It consists of an extracellular domain of 370 amino acids, a short transmembrane region, and a cytoplasmic domain of 40 amino acids at the C-terminal end. We investigated the structure of the 62 C-terminal residues of CD4, comprising its transmembrane and cytoplasmic domains. The five cysteine residues of this region have been replaced with serine and histidine residues in the polypeptide CD4mut. Uniformly 15N and 13C labeled protein was recombinantly expressed in E. coli and purified. Functional binding activity of CD4mut to protein VpU of the human immunodeficiency virus type 1 (HIV-1) was verified. Close to complete NMR resonance assignment of the 1H, 13C, and 15N spins of CD4mut was accomplished. The secondary structure of CD4mut in membrane simulating dodecylphosphocholine (DPC) micelles was characterized based on secondary chemical shift analysis, NOE-based proton-proton distances, and circular dichroism spectroscopy. A stable transmembrane helix and a short amphipathic helix in the cytoplasmic region were identified. The fractional helicity of the cytoplasmic helix appears to be stabilized in the presence of DPC micelles, although the extension of this helix is reduced in comparison to previous studies on synthetic peptides in aqueous solution. The role of the amphipathic helix and its potentially variable length is discussed with respect to the biological functions of CD4.
KW  - Amino Acid Sequence
KW  - Antigens, CD4: chemistry
KW  - Antigens, CD4: genetics
KW  - Antigens, CD4: metabolism
KW  - Carbon Isotopes
KW  - Circular Dichroism
KW  - Human Immunodeficiency Virus Proteins: metabolism
KW  - Humans
KW  - Magnetic Resonance Spectroscopy: methods
KW  - Models, Molecular
KW  - Molecular Sequence Data
KW  - Mutation
KW  - Nitrogen Isotopes
KW  - Protein Binding
KW  - Protein Structure, Secondary
KW  - Protein Structure, Tertiary
KW  - Viral Regulatory and Accessory Proteins: metabolism
KW  - Antigens, CD4 (NLM Chemicals)
KW  - Carbon Isotopes (NLM Chemicals)
KW  - Human Immunodeficiency Virus Proteins (NLM Chemicals)
KW  - Nitrogen Isotopes (NLM Chemicals)
KW  - Viral Regulatory and Accessory Proteins (NLM Chemicals)
KW  - J (WoSType)
LB  - PUB:(DE-HGF)16
C6  - pmid:18035040
UR  - <Go to ISI:>//WOS:000252488900002
DO  - DOI:10.1016/j.bbamem.2007.10.023
UR  - https://juser.fz-juelich.de/record/60128
ER  -