Home »

Ccr5

The meaning of «ccr5»

C-C chemokine receptor type 5, also known as CCR5 or CD195, is a protein on the surface of white blood cells that is involved in the immune system as it acts as a receptor for chemokines.[5]

In humans, the CCR5 gene that encodes the CCR5 protein is located on the short (p) arm at position 21 on chromosome 3. Certain populations have inherited the Delta 32 mutation, resulting in the genetic deletion of a portion of the CCR5 gene. Homozygous carriers of this mutation are resistant to M-tropic strains of HIV-1 infection.[6][7][8][9][10][11]

The CCR5 protein belongs to the beta chemokine receptors family of integral membrane proteins.[12][13] It is a G protein–coupled receptor[12] which functions as a chemokine receptor in the CC chemokine group.

CCR5's cognate ligands include CCL3, CCL4 (also known as MIP 1α and 1β, respectively), and CCL3L1.[14][15] CCR5 furthermore interacts with CCL5 (a chemotactic cytokine protein also known as RANTES).[14][16][17]

CCR5 is predominantly expressed on T cells, macrophages, dendritic cells, eosinophils, microglia and a subpopulation of either breast or prostate cancer cells.[18][19] The expression of CCR5 is selectively induced during the cancer transformation process and is not expressed in normal breast or prostate epithelial cells. Approximately 50% of human breast cancer expressed CCR5, primarily in triple negative breast cancer.[18] CCR5 inhibitors blocked the migration and metastasis of breast and prostate cancer cells that expressed CCR5, suggesting that CCR5 may function as a new therapeutic target.[18][19][20] Recent studies suggest that CCR5 is expressed in a subset of cancer cells with characteristics of cancer stem cells, which are known to drive therapy resistance, and that CCR5 inhibitors enhanced the number of cells killed by current chemotherapy.[21] It is likely that CCR5 plays a role in inflammatory responses to infection, though its exact role in normal immune function is unclear. Regions of this protein are also crucial for chemokine ligand binding, the functional response of the receptor, and HIV co-receptor activity.[22]

HIV-1 most commonly uses the chemokine receptors CCR5 and/or CXCR4 as co-receptors to enter target immunological cells.[23] These receptors are located on the surface of host immune cells whereby they provide a method of entry for the HIV-1 virus to infect the cell.[24] The HIV-1 envelope glycoprotein structure is essential in enabling the viral entry of HIV-1 into a target host cell.[24] The envelope glycoprotein structure consists of two protein subunits cleaved from a Gp160 protein precursor encoded for by the HIV-1 env gene: the Gp120 external subunit and the Gp41 transmembrane subunit.[24] This envelope glycoprotein structure is arranged into a spike-like structure located on the surface of the virion and consists of a trimer of Gp120-Gp41 hetero-dimers.[24] The Gp120 envelope protein is a chemokine mimic.[23] Though it lacks the unique structure of a chemokine, it is still capable of binding to the CCR5 and CXCR4 chemokine receptors.[23] During HIV-1 infection, the Gp120 envelope glycoprotein subunit binds to a CD4 glycoprotein and a HIV-1 co-receptor expressed on a target cell, forming a heterotrimeric complex.[23] The formation of this complex stimulates the release of a fusogenic peptide, causing the viral membrane to fuse with the membrane of the target host cell.[23] Because binding to CD4 alone can sometimes result in gp120 shedding, gp120 must next bind to co-receptor CCR5 in order for fusion to proceed. The tyrosine-sulfated amino terminus of this co-receptor is the "essential determinant" of binding to the gp120 glycoprotein.[25] The co-receptor also recognizes the V1-V2 region of gp120 and the bridging sheet (an antiparallel, 4-stranded β sheet that connects the inner and outer domains of gp120). The V1-V2 stem can influence "co-receptor usage through its peptide composition as well as by the degree of N-linked glycosylation." Unlike V1-V2 however, the V3 loop is highly variable and thus is the most important determinant of co-receptor specificity.[25] The normal ligands for this receptor, RANTES, MIP-1β, and MIP-1α, are able to suppress HIV-1 infection in vitro. In individuals infected with HIV, CCR5-using viruses are the predominant species isolated during the early stages of viral infection,[26] suggesting that these viruses may have a selective advantage during transmission or the acute phase of disease. Moreover, at least half of all infected individuals harbor only CCR5-using viruses throughout the course of infection.

Related Searches

CCR5 receptor antagonistCCR2CCRL Refinery Complex
CCRCCR3 (gene)CCR1
CCR8 (gene)CCL5CCR4

Choice of words

c-c-r5_ _
c-c-r5_ _
ccr-5_ _
ccr5:_ _ _ _
ccr5_ _ _ _
ccr5_ - _ _ _
ccr5-_ _ _ _
ccr5 _ _ _ _ _
ccr5 _ - _ _ _ _
© 2015-2020, Wikiwordbook.info
Copying information without reference to the source is prohibited!
contact us mobile version