| General information | | DisProt: | DP00123 | | Name: | T-cell surface glycoprotein CD4 | | Synonym(s): | CD4_HUMAN
T-cell surface antigen T4/Leu-3
| | First appeared in release: | Release 3.0 (02/17/2006) | | UniProt: | P01730 | | UniGene: | Hs.631659 | | SwissProt: | CD4_HUMAN | | TrEMBL: | | | NCBI (GI): | 116013 | | Source organism: | Homo sapiens (Human) | | Sequence length: | 458 | | Percent disordered: | 8% | | Homologues: | |
| Native sequence |
10 20 30 40 50 60
| | | | | |
MNRGVPFRHL LLVLQLALLP AATQGKKVVL GKKGDTVELT CTASQKKSIQ FHWKNSNQIK - 60
ILGNQGSFLT KGPSKLNDRA DSRRSLWDQG NFPLIIKNLK IEDSDTYICE VEDQKEEVQL - 120
LVFGLTANSD THLLQGQSLT LTLESPPGSS PSVQCRSPRG KNIQGGKTLS VSQLELQDSG - 180
TWTCTVLQNQ KKVEFKIDIV VLAFQKASSI VYKKEGEQVE FSFPLAFTVE KLTGSGELWW - 240
QAERASSSKS WITFDLKNKE VSVKRVTQDP KLQMGKKLPL HLTLPQALPQ YAGSGNLTLA - 300
LEAKTGKLHQ EVNLVVMRAT QLQKNLTCEV WGPTSPKLML SLKLENKEAK VSKREKAVWV - 360
LNPEAGMWQC LLSDSGQVLL ESNIKVLPTW STPVQPMALI VLGGVAGLLL FIGLGIFFCV - 420
RCRHRRRQAE RMSQIKRLLS EKKTCQCPHR FQKTCSPI
|
| Functional narrative |
The human T cell receptor CD4 is a 55 kDa type I integral membrane glycoprotein that is involved
in T cell activation and also acts as the primary coreceptor for human immunodeficiency viruses (HIV). It is expressed on the surface
of a subset of T lymphocytes that recognize MHC1 class II
presented antigens (Ag). The human
CD4 molecule is comprised of a 395 amino acid extracellular
(CD4ECTO) domain, a single 25 amino acid transmembrane
(CD4TM) anchor, and a cytoplasmic (CD4CYTO) tail of 38
amino acids. CD4CYTO tail, this membrane-proximal region has important
biological functions. First, following interaction of the
CD4ECTO domain with the MHC class II Ag-TCR complex,
the activation cascade of T cell response is transmitted to
the cytoplasm via noncovalent binding of the CD4CYTO tail
with the tyrosine kinase p56lck, a member of the src family
of cytosolic tyrosine kinases. Both stimulation by Ag exposure and treatment
with phorbol ester induce protein kinase-dependent phosphorylation
of three serine residues in the CD4CYTO tail
which triggers dissociation of p56lck from CD4 followed by
internalization and lysosomal degradation of CD4. Second, another important function of the CD4CYTO tail is
the interaction with the HIV accessory proteins Nef and Vpu
occurring in the complex process of HIV receptor interference.
|
| Map of ordered and disordered regions |
Note: 'Mouse' over a region to see the start and stop residues. Click on a region to see detailed information.
|
| Region 1 | | Type: | Disordered | | Name: | cytoplasmic tail | | Location: | 421 - 458 | | Length: | 38 | | Region sequence: |
RCRHRRRQAERMSQIKRLLSEKKTCQCPHRFQKTCSPI | | Modification type: | Fragment
Native
| | PDB: | | | Structural/functional type: | Function arises via a disorder to order transition
| | Functional classes: | Molecular recognition effectors
| | Functional subclasses: | Protein-protein binding
| Detection methods:
- Circular dichroism (CD) spectroscopy, far-UV (298 K; )
- Nuclear magnetic resonance (NMR) (300 K; pH: 1.9; 0.3 mg 1,4-dithiothreitol; 9 mg peptide in 600 microl 50% TFE-d2)
| References:
- Wray V, Mertins D, Kiess M, Henklein P, Trowitzsch-Kienast W, Schubert U. "Solution structure of the cytoplasmic domain of the human CD4 glycoprotein by CD and 1H NMR spectroscopy: implications for biological functions." Biochemistry. 1998; 37(23): 8527-38. PubMed: 9622505
| Comments:CD and NMR results in aqueous solution were characteristic of a
disordered peptide conformation with very little evidence of
stable secondary structure. However,
both the qualitative and quantitative NMR data provide
convincing evidence for the presence of predominantly
alfa-helical secondary structure upon increasing the content of
TFE, but only a fraction of the complete CD4CYTO tail (from Gln-428 to Arg-437)
has the ability of adopting stabilized helical structure in this
environment. The N- and
C-terminal regions, which are inherently nonstructured,
destabilize the alfa-helical core structure. Addition of TFE causes a stabilization of the helical
region in the molecule that already has a tendency for such
a structure when this helical region of CD4CYTO was studied
in water alone. However, in the context of full-length
CD4CYTO, the helical core structure requires stabilizing factors
which could be provided either by the membrane itself or
by other CD4 interacting factors such as Vpu, Nef, or p56lck.
|
| References |
- Konig R, Zhou W. "Signal transduction in T helper cells: CD4 coreceptors exert complex regulatory effects on T cell activation and function." Curr Issues Mol Biol. 2004; 6(1): 1-15. PubMed: 14632255
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