CD4 Molecule
T-cell surface glycoprotein CD4 (T-cell antigen T4/leu3) is a single-pass type I membrane protein with four immunoglobulin-like extra-cellular N-terminal domains and a short C-terminal cytoplasmic domain. It is a 55 kDa, 433 amino acids long processed protein coded by the CD4 gene (Gene map locus 12p13.31) that is post-translationally modified by S-palmitoylation on Cys419(Cys394) and Cys422(Cys397) and N-linked glycosylation at Asn296(Asn271) and Asn325(Asn297). Palmitoylation and association with LCK contribute to the enrichment of CD4 in lipid rafts.
CD4, T-cell surface antigen T4, is a T cell receptor (TCR) co-receptor that augments early phase antigen-induced T-cell signaling on helper, regulatory, inducer T cells. CD4 is a class II major histocompatibility complex (MHC-II) restricted molecule that interacts with the relatively invariant beta2-domain of MHC-II molecules associated with antigen presenting cells (APC). It does not interact with MHC-I. The cytoplasmic tail of CD4 interacts with LCK, a CD3-zeta kinase, to induce cell signaling. Alternatively, CD4 can bind to focal adhesion kinase (FAK). Interaction of ACP33 with the cytoplasmic tail of CD4 negatively regulates CD4. CD4 binds both directly and indirectly with a significant number of other signaling regulators and cytoskeletal components.
The expression of CD4 by other cells such as B-cells, dendritic cells (DC), macrophages, granulocytes and microglia (resident mononuclear phagocytes of the brain) suggests that CD4 may play a broader role in cell:cell interaction than T-cell receptor activation.
Interest in CD4 is driven significantly by the finding that CD4 positive T-cells are the primary target for human immunodeficiency virus (HIV), the AIDS virus. CD4 is the primary receptor for the HIV-1 viral envelop-protein, gp120. Binding of gp120 to CD4 induces a conformational change that allows gp120 to bind to the chemokine receptors, CCR5 or CXCR4. These receptors act as co-receptors during the initial stages of infection. A second HIV-1 protein, gp41, inserts a fusion peptide that results in viral and cell membrane fusion and infection.
Interest in CD4 as a co-receptor for T-cell response to antigen presentation, for studies of cell:cell interactions and for an understanding of the process of AIDS infection have lead to over 85,000 abstract citations in NCBI’s PubMed.
Sigma offers antibodies, shRNAs and other products useful for the study of the CD4 gene.
References:
Berger EA, Alkhatib G. (2007) HIV gp120 interactions with coreceptors: insights from studies with CCR5-based peptides. Eur J Med Res.12: 403-407.
Copeland KF. (2006) Inhibition of HIV-1 entry into cells. Recent Patents Anti-Infect Drug Disc. 1: 107-112.
Garron ML, Arthos J, Guichou JF, McNally J, Cicala C, Arold ST. (2008) Structural basis for the interaction between focal adhesion kinase and CD4. J Mol Biol. 375: 1320-1328.
Krotov GI, Krutikova MP, Zgoda VG, Filatov AV. (2007) Profiling of the CD4 receptor complex proteins. Biochemistry (Mosc) 72: 1216-1224
König R. (2002) Interactions between MHC molecules and co-receptors of the TCR. Curr. Opin. Immunol. 14: 75-83.
Footnote: Gene Data Sources: HGNC, Entrez Gene, UniProt/Swiss-Prot, UniProt/TrEMBL, GDB, OMIM, GeneLoc, Ensembl.
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