Introduction of CCR-5
CCR-5 (designated as CD195), is a membrane receptor protein encoded by CCR5 gene which is found in human immune cells such as monocytes and lymphocytes. CCR-5 is highly expressed in spleen, thymus, in the myeloid cell line THP-1, in the promyeloblastic cell line KG-1a and on CD4+ and CD8+ T-cells. It belongs to the G-protein-coupled receptor family, which is involved in the immune system as it functions as a receptor for chemokines. CCR-5 is a receptor for several inflammatory CC chemokines including MIP-1-alpha, MIP-1-beta, and RANTES.
|Basic Information of CCR-5|
|Protein Name||C-C chemokine receptor type 5|
|Aliases||CHEMR13, HIV-1 fusion coreceptor, CD195, CC-CKR-5|
|Organism||Homo sapiens (Human)|
Function of CCR-5 Membrane Protein
As binding with its various ligands, CCR-5 subsequently transduces a signal by up-regulating the intracellular calcium ion level. This receptor may also play a role in the control of granulocytic lineage proliferation or differentiation. CCR-5 acts as a co-receptor of HIV R5 isolates, which causes AIDS. It cooperates with the host cellular CD4 protein (the primary receptor for HIV) to permit the initial docking of the HIV virus onto T-cells and subsequent infection. The CD4 bound HIV envelope spike protein to utilize CCR-5 as a co-receptor to enter and infect host cells. Consequently, CCR5 antagonist development has suggested to be a very effective therapeutic method. CCR-5 has also been regarded as an essential node in the bidirectional communication between breast cancer and normal cells. Specifically, the CCL5/CCR5 axis is involved in the recruitment of specific immune cells into tumors, inducing local immunosuppression and promoting tumor progression, which supports the use of CCR5 antagonists in breast cancer patients as adjuvant therapy to block the metastasis.
Application of CCR-5 Membrane Protein in Literature
1. Jin J., et al. CCR5 adopts three homodimeric conformations that control cell surface delivery. Sci Signal. 2018, 1(529). pii: eaal2869. PubMed ID: 29739880
This article suggests that dimerization of CCR5 contributes to the conformational diversity of inactive class A GPCRs and may provide new opportunities to investigate the cellular entry of HIV-1 and mechanisms for its inhibition.
2. Wu Y.C., et al. Autocrine CCL5 promotes tumor progression in esophageal squamous cell carcinoma in vitro. Cytokine. 2018, 110: 94-103. PubMed ID: 29705397
This article focused on the pro-tumoral effects of CCL5 and reveals that that CCL5 autocrine loop may promote ESCC progression; targeting the CCL5/CCR5 axis could be a potential therapeutic strategy for this deadly disease.
3. Lee D., et al. CCL4 enhances preosteoclast migration and its receptor CCR5 downregulation by RANKL promotes osteoclastogenesis. Cell Death Dis. 2018, 9(5): 495. PubMed ID: 29717113
Authors in this group we investigated the function of CCL4 and its receptor CCR5 during osteoclastogenesis and the results indicated that CCL4 can enhance the recruitment of preosteoclasts to bones in the early stage, and the reduction of CCR5 promotes osteoclastogenesis when RANKL is prevalent.
4. Petti L.M., et al. Regulation of C-C chemokine receptor 5 (CCR5) stability by Lys-197 and by transmembrane protein aptamers that target it for lysosomal degradation. J Biol Chem. 2018, pii: jbc.RA117.001067. PubMed ID: 29678881
This article focuses on the mechanism of traptamer-mediated CCR5 down-regulation and shows that most of the traptamers (designated class 1 traptamers) form a stable complex with CCR5 and target it for lysosome-mediated degradation.
5. Hütter G., et al. CCR5 Targeted Cell Therapy for HIV and Prevention of Viral Escape. Viruses. 2015, 7(8): 4186-203. PubMed ID: 26225991
This article focuses on the current knowledge of inhibition of CCR5 specifically and whether this approach allows for consequent viral escape.
CCR-5 Preparation Options
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