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Credit: Raymond Stevens
Scripps Research Institute
A team of researchers has uncovered the structure of a cell surface receptor, CXCR4, which guides blood and immune cell movement throughout the body.
CXCR4 is also found on the surface of the human immunodeficiency virus (HIV), and helps the virus to enter blood cells.
The receptor is part of a group of about 700 proteins known as G protein-coupled receptors (GPCRs).
The team, led by Raymond C. Stevens, PhD, of Scripps Research Institute in La Jolla, California, and senior author of the study, already found the structures of two other GPCRs: the adrenergic receptor and A2A adenosine receptor.
CXCR4 belongs to a different group of GPCRs, one that binds to protein molecules called chemokines, responsible for steering blood and immune cells where they are needed.
The team used GPCR biochemistry, receptor stabilization, and X-ray crystallography to capture the first visual of a chemokine receptor bound to a ligand.
Unlike the adrenergic receptor and the A2A adenosine receptor, CXCR4 likes to form dimers.
“The dimerization observation was very intriguing,” said Dr Stevens. “We solved 5 different crystal structures in multiple crystal forms, and each one had the same dimer interface. It has long been debated how GPCRs might dimerize, if they did at all. This is the first solid observation about a consistent structural GPCR dimer.”
The team believes preventing dimerization might provide a new way to block CXCR4, which results in the release of hematopoietic stem cells from bone marrow into the bloodstream.
Currently, plerixafor injection is the only drug on the market that blocks CXCR4. Therapy that assists in the release of hematopoietic stem cells to the bloodstream is very useful following stem cell transplant.
Drugs that block CXCR4 are also useful in treating HIV infection.
Their findings were published in the October 7 issue of Science. 
Credit: Raymond Stevens
Scripps Research Institute
A team of researchers has uncovered the structure of a cell surface receptor, CXCR4, which guides blood and immune cell movement throughout the body.
CXCR4 is also found on the surface of the human immunodeficiency virus (HIV), and helps the virus to enter blood cells.
The receptor is part of a group of about 700 proteins known as G protein-coupled receptors (GPCRs).
The team, led by Raymond C. Stevens, PhD, of Scripps Research Institute in La Jolla, California, and senior author of the study, already found the structures of two other GPCRs: the adrenergic receptor and A2A adenosine receptor.
CXCR4 belongs to a different group of GPCRs, one that binds to protein molecules called chemokines, responsible for steering blood and immune cells where they are needed.
The team used GPCR biochemistry, receptor stabilization, and X-ray crystallography to capture the first visual of a chemokine receptor bound to a ligand.
Unlike the adrenergic receptor and the A2A adenosine receptor, CXCR4 likes to form dimers.
“The dimerization observation was very intriguing,” said Dr Stevens. “We solved 5 different crystal structures in multiple crystal forms, and each one had the same dimer interface. It has long been debated how GPCRs might dimerize, if they did at all. This is the first solid observation about a consistent structural GPCR dimer.”
The team believes preventing dimerization might provide a new way to block CXCR4, which results in the release of hematopoietic stem cells from bone marrow into the bloodstream.
Currently, plerixafor injection is the only drug on the market that blocks CXCR4. Therapy that assists in the release of hematopoietic stem cells to the bloodstream is very useful following stem cell transplant.
Drugs that block CXCR4 are also useful in treating HIV infection.
Their findings were published in the October 7 issue of Science.
Credit: Raymond Stevens
Scripps Research Institute
A team of researchers has uncovered the structure of a cell surface receptor, CXCR4, which guides blood and immune cell movement throughout the body.
CXCR4 is also found on the surface of the human immunodeficiency virus (HIV), and helps the virus to enter blood cells.
The receptor is part of a group of about 700 proteins known as G protein-coupled receptors (GPCRs).
The team, led by Raymond C. Stevens, PhD, of Scripps Research Institute in La Jolla, California, and senior author of the study, already found the structures of two other GPCRs: the adrenergic receptor and A2A adenosine receptor.
CXCR4 belongs to a different group of GPCRs, one that binds to protein molecules called chemokines, responsible for steering blood and immune cells where they are needed.
The team used GPCR biochemistry, receptor stabilization, and X-ray crystallography to capture the first visual of a chemokine receptor bound to a ligand.
Unlike the adrenergic receptor and the A2A adenosine receptor, CXCR4 likes to form dimers.
“The dimerization observation was very intriguing,” said Dr Stevens. “We solved 5 different crystal structures in multiple crystal forms, and each one had the same dimer interface. It has long been debated how GPCRs might dimerize, if they did at all. This is the first solid observation about a consistent structural GPCR dimer.”
The team believes preventing dimerization might provide a new way to block CXCR4, which results in the release of hematopoietic stem cells from bone marrow into the bloodstream.
Currently, plerixafor injection is the only drug on the market that blocks CXCR4. Therapy that assists in the release of hematopoietic stem cells to the bloodstream is very useful following stem cell transplant.
Drugs that block CXCR4 are also useful in treating HIV infection.
Their findings were published in the October 7 issue of Science.