Hello Dr. Vipul Navadiya,
I looked into this site because I wanted to understand more about the G protein receptor. I'm invested in CytoDyn, or CYDY on OTC exchange. I'm interested in a certain monoclonal antibody, Leronlimab, which binds to CCR5, which is a G protein receptor. The companies are calling it a CCR5 "blocker", but maybe it acts more like a binder. As it binds to the receptor very well with strong affinity. As it is a monoclonal antibody, it is larger, but I do not believe it affects any conformational changes in the g protein CCR5. Leronlimab has been shown very effective in knocking down HIV load and preventing AIDS in over 8 years of use in patients by working as an HIV entry inhibitor. In cancer, it prevents RANTES from binding to CCR5 so the Tumor cannot metastasize. It seems that Leronlimab is more of a RANTES or CCL5 blocker than a receptor blocker.
What I don't understand is why when a ligand like Leronlimab binds to the CCR5 receptor, the same effects don't happen as when the RANTES ligand binds to the same CCR5 receptor?
I don't know if you've studied Leronlimab, but its affinity for CCR5 is very strong, so I was curious, do you know if it knocks RANTES out of the receptor and replaces RANTES with itself?
CCR5 is supposed to do with the kinetics of the cell, it is supposed to tell the cell where to travel. By doing so, inflammation somehow is reduced.
Do you know anything about why the G proteins may be internalized to the interior of the cell and then they may later be re-expressed on the cell surfaces? Somehow in Long Haulers, these CCR5 G proteins are hardly expressed on the cell surfaces. Does RANTES have some thing to do with paralyzing the cells? It seems as if when these CCR5 receptors are bound with CCL5, the cell is found to be paralyzed, unable to do its job. It doesn't know what to do. It just sits there helpless. But when Leronlimab is added again, the CCR5 move back out to the cell surfaces and the cell comes back to life doing what it was supposed to do all the time.
thank you so much Dr. Vipul Navadiya for your reply,
You wrote:
“Receptor Internalization is cells' response to prevent overstimulation of receptor. “
Can I ask then, why would it be that when a ligand drug has 100% receptor occupancy to it’s G-Protein receptor, how is it then that those receptors do not internalize?
On the topic of G Protein Receptors, lets talk even more specifically, the CCR5 G protein receptor, Do all CCR5 G protein Receptors have the same sub units? alpha, beta and gamma? Do all CCR5 have Gs, Gi, Go and Gq?
If a T Cell has many CCR5 G proteins on its surface, will all the CCR5 G proteins have the same sub units or could some CCR5 have Gs while other CCR5 have Go, etc...?
So, I guess what I'm asking, is CCR5 G Protein made up of specific G protein subunits, or could different CCR5 have different G protein subunits while having the same Receptor Binding site?
Are the CCR5 G Protein Receptors different based on the cell they are on the surface of? Like, are the CCR5 Receptors on the surfaces of Hepatocytes, the same as the CCR5 Receptors on the islet cells of the pancreas?
Does the CCR5 Receptor have a Monomeric G protein? or is it only the Heterotrimeric?
Is there a way to know exactly what happens when a ligand binds to the receptor of the CCR5 receptor? Does this functionality differ between the various cells the CCR5 receptor is found on?
Is there a way to know how each cell type behaves or is effected when CCR5 is bound by certain ligands?
You definitely have way deeper knowledge about CCR5 and Leronlimab than I do. What I can add are general points. You might already be knowing this, but, here it is...
What I don't understand is why when a ligand like Leronlimab binds to the CCR5 receptor, the same effects don't happen as when the RANTES ligand binds to the same CCR5 receptor?Different ligands can produce different conformational changes in receptors. And based on that the response may be different.
I don't know if you've studied Leronlimab, but its affinity for CCR5 is very strong, so I was curious, do you know if it knocks RANTES out of the receptor and replaces RANTES with itself?If it has a high affinity then it's possible.
Do you know anything about why the G proteins may be internalized to the interior of the cell and then they may later be re-expressed on the cell surfaces?Receptor Internalization is cells' response to prevent overstimulation of receptor.
I hope it helps.