CCR5 Protein
Overview
<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">CCR5 Protein</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td>CCR5</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>C-C Chemokine Receptor Type 5</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>3p21.31</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>1234</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000160791</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td>P51681</td>
</tr>
<tr>
<td class="label">Agent</td>
<td>Mechanism</td>
</tr>
<tr>
<td class="label">Maraviroc</td>
<td>CCR5 antagonist</td>
</tr>
<tr>
<td class="label">Vicriviroc</td>
<td>CCR5 antagonist</td>
</tr>
<tr>
<td class="label">Aplaviroc</td>
<td>CCR5 antagonist</td>
</tr>
<tr>
<td class="label">CCR5 antibodies</td>
<td>Neutralizing antibodies</td>
</tr>
<tr>
<td class="label">CCR5-targeting siRNA</td>
<td>Gene silencing</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/autoimmune" style="color:#ef9a9a">Autoimmune</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/cardiovascular" style="color:#ef9a9a">Cardiovascular</a>, <a href="/wiki/dementia" style="color:#ef9a9a">Dementia</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">109 edg
...CCR5 Protein
Overview
<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">CCR5 Protein</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td>CCR5</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>C-C Chemokine Receptor Type 5</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>3p21.31</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>1234</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000160791</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td>P51681</td>
</tr>
<tr>
<td class="label">Agent</td>
<td>Mechanism</td>
</tr>
<tr>
<td class="label">Maraviroc</td>
<td>CCR5 antagonist</td>
</tr>
<tr>
<td class="label">Vicriviroc</td>
<td>CCR5 antagonist</td>
</tr>
<tr>
<td class="label">Aplaviroc</td>
<td>CCR5 antagonist</td>
</tr>
<tr>
<td class="label">CCR5 antibodies</td>
<td>Neutralizing antibodies</td>
</tr>
<tr>
<td class="label">CCR5-targeting siRNA</td>
<td>Gene silencing</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/autoimmune" style="color:#ef9a9a">Autoimmune</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/cardiovascular" style="color:#ef9a9a">Cardiovascular</a>, <a href="/wiki/dementia" style="color:#ef9a9a">Dementia</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">109 edges</a></td>
</tr>
</table>
Ccr5 Protein plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.
Introduction
CCR5 (C-C Chemokine Receptor Type 5) is a G protein-coupled receptor that serves as a major co-receptor for HIV-1 entry and plays crucial roles in immune cell trafficking and neuroinflammation. As a chemokine receptor, CCR5 mediates the recruitment of immune cells to sites of inflammation and is expressed on various cell types in the central nervous system, including [microglia](/cell-types/microglia-neuroinflammation) and astrocytes. Dysregulation of CCR5 signaling contributes to chronic neuroinflammation in neurodegenerative diseases, making it both a therapeutic target and a modulator of disease progression. [@zhou2019]
Protein Structure
CCR5 is a 352-amino acid G protein-coupled receptor (GPCR) with characteristic seven-transmembrane domain architecture:
- Molecular weight: ~46 kDa
- Structure: 7 transmembrane α-helices connected by 3 extracellular and 3 intracellular loops
- N-terminus: Extracellular, heavily glycosylated
- C-terminus: Intracellular, involved in G protein coupling
- Extracellular loops (ECL1-3): Contain ligand binding sites
- Intracellular loops (ICL1-3): Couple to G proteins
The crystal structure (PDB: 5UIW) reveals the binding pockets for both endogenous chemokines and small molecule antagonists like maraviroc. The receptor exists as a monomer and can form homodimers or heterodimers with other chemokine receptors.
Molecular Function
CCR5 functions as a chemokine receptor through the following mechanisms:
Ligand Binding: Binds multiple CC chemokines including:
- CCL3 (MIP-1α)
- CCL4 (MIP-1β)
- CCL5 (RANTES)
- CCL3L1 (MIP-1β)
Signal Transduction:
- Gαi protein-coupled signaling
- Inhibition of adenylate cyclase
- Activation of MAPK/ERK pathway
- PI3K/Akt signaling
Cellular Effects:
- Chemotaxis and cell migration
- Immune cell activation
- Cytokine production
- Cell survival and proliferation
Viral Co-receptor Function:
- Primary co-receptor for R5-tropic HIV-1
- Entry mechanism for viral fusion
- Target for HIV prevention strategies
Expression Pattern
CCR5 is expressed on multiple cell types:
Immune Cells:
- T lymphocytes (memory CD4+ and CD8+ T cells)
- Monocytes/macrophages
- Dendritic cells
- Natural killer cells
Central Nervous System:
- [Microglia](/entities/microglia) (highly expressed)
- [Astrocytes](/entities/astrocytes) (reactive astrocytes)
- [Neurons](/entities/neurons) (low expression)
- Endothelial cells
In the brain, CCR5 expression increases during neuroinflammation, with highest expression on activated microglia surrounding amyloid plaques in Alzheimer's disease and in the substantia nigra in Parkinson's disease.
Role in Neurodegenerative Diseases
Alzheimer's Disease
- Elevated CCR5 expression in AD brain tissue, particularly in microglia
- Promotes chronic neuroinflammation through continued immune cell recruitment
- Contributes to microglial activation and pro-inflammatory cytokine release
- Genetic variants (CCR5-Δ32) may modify AD risk and age of onset
- CCR5 signaling may interact with [amyloid-beta](/proteins/amyloid-beta) pathology
Parkinson's Disease
- Increased CCR5 expression in substantia nigra dopaminergic neurons
- Mediates inflammatory responses in the nigrostriatal pathway
- May influence dopaminergic neuron degeneration
- CCL5/CCR5 axis implicated in PD pathogenesis
- Therapeutic targeting potential for neuroprotection
HIV-Associated Neurocognitive Disorders (HAND)
- Primary co-receptor for R5-tropic HIV-1 infection of microglia/macrophages
- HIV proteins (gp120, Tat) can dysregulate CCR5 signaling
- Neuroinflammation driven by viral proteins through CCR5
- CCR5 antagonists may reduce HIV-associated neurotoxicity
- Chronic inflammation persists despite antiretroviral therapy
Multiple Sclerosis
- CCR5+ T cells infiltrate demyelinating lesions
- Contributes to autoimmune inflammation in CNS
- CCL5 levels elevated in MS lesions and cerebrospinal fluid
- CCR5 blockade may reduce demyelination and disease progression
- Genetic variants associated with MS susceptibility
Amyotrophic Lateral Sclerosis
- CCR5 expression increased in ALS spinal cord
- Microglial activation mediated by CCR5 signaling
- Contributes to neuroinflammation in motor neuron disease
Therapeutic Targeting
Neurological Applications:
- Potential for neuroprotection in AD and PD
- May reduce microglial-mediated inflammation
- Combination with antiretroviral therapy for HAND
Animal Models
- Ccr5 knockout mice: Viable, altered immune cell trafficking
- Transgenic mice: CCR5 overexpression in CNS
- MPTP model: CCR5 deletion reduces neuroinflammation
- [APP](/entities/app-protein)/PS1 model: CCR5 deficiency affects amyloid pathology
Overview
Ccr5 Protein plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.
Background
The study of Ccr5 Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
See Also
- [CCR5 Gene](/genes/ccr5) - Gene page
- [Neuroinflammation Pathway](/mechanisms/neuroinflammation) - Related mechanism
- [Alzheimer's Disease](/diseases/alzheimers-disease) - Disease association
- [Parkinson's Disease](/diseases/parkinsons-disease) - Disease association
- [HIV-Associated Neurocognitive Disorders](/diseases/hiv-associated-neurocognitive-disorders) - Disease association
- [Multiple Sclerosis](/diseases/multiple-sclerosis) - Disease association
- [CCL3 Protein](/proteins/ccl3-protein) - Ligand
- [CCL4 Protein](/proteins/ccl4-protein) - Ligand
- [CCL5 Protein](/proteins/ccl5) - Ligand
- [Microglia](/cell-types/microglia) - Cell type
- [Astrocytes](/cell-types/astrocytes) - Cell type
External Links
- [UniProt: P51681](https://www.uniprot.org/uniprot/P51681)
- [PDB: 5UIW](https://www.ebi.ac.uk/pdbe/entry/pdb/5uiw)
- [IUPHAR: CCR5](https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=68)
- [NCBI Gene: CCR5](https://www.ncbi.nlm.nih.gov/gene/1234)
- [Human Protein Atlas: CCR5](https://www.proteinatlas.org/ENSG00000160791-CCR5)
References
[Lim JK et al, (2020) (2020)](https://pubmed.ncbi.nlm.nih.gov/33168027/)
[Zhou Y et al, (2019) (2019)](https://pubmed.ncbi.nlm.nih.gov/31759012/)
[Bakhiet M et al, (2017) (2017)](https://pubmed.ncbi.nlm.nih.gov/28757481/)
[Conductier G et al, (2015) (2015)](https://pubmed.ncbi.nlm.nih.gov/26306872/)
[Mallard J et al, (2014) (2014)](https://pubmed.ncbi.nlm.nih.gov/25218854/)
[Szepanski Z et al, (2013) (2013)](https://pubmed.ncbi.nlm.nih.gov/23934690/)
[Galimberti D et al, (2012) (2012)](https://pubmed.ncbi.nlm.nih.gov/22503163/)