User login
attached to syncytiotrophoblast
Credit: Fabio T.M. Costa
Plasmodium vivax malaria attacks red blood cells by clamping down on the cells with a pair of proteins, researchers have found.
Earlier studies suggested that a single P vivax protein binds to a protein on the surface of red blood cells.
But the new study showed that binding is a 2-step process that involves 2 copies of a parasite protein coming together like tongs around 2 copies of a host protein.
The researchers believe this discovery, detailed in PLOS Pathogens, could help scientists design better vaccines and treatments for P vivax, which is common in India, Southeast Asia, and South America.
“More people live at risk of infection by this strain of malaria than any other,” said senior study author Niraj Tolia, PhD, of the Washington University School of Medicine in St Louis, Missouri.
“We now are using what we have learned to create vaccines tailored to stop the infectious process by preventing the parasite from attaching to red blood cells.”
Dr Tolia and his colleagues knew that P vivax Duffy binding protein (DBP) recognizes the receptor Duffy antigen/receptor for chemokines (DARC) during the parasite’s invasion of red blood cells. But the team wanted to identify binding contacts during invasion and determine the molecular basis of DBP receptor recognition.
So they conducted structural studies on the minimal binding domain of DBP in complex with the minimal region from DARC. And they found that 2 DBP molecules bind 2 DARC molecules.
The researchers also performed erythrocyte binding assays with binding site mutants and identified essential receptor contacts.
“It’s a very intricate and chemically strong interaction that was not easily understood before,” Dr Tolia said. “We have had hints that other forms of malaria, including the African strain, may be binding in a similar fashion to host cells, but this is one of the first definitive proofs of this kind of attack.”
Dr Tolia suspects that blocking any of the proteins with drugs or vaccines will stop the infectious process.
“For example, some people have a mutation that eliminates the protein on red blood cell surfaces that P vivax binds to, and they tend to be resistant to the parasite,” he said. “This is why this strain isn’t prevalent in Africa. Evolutionary pressure has caused most of the populations there to stop making this protein.”
Dr Tolia and his colleagues also found evidence that other people with immunity to P vivax have developed naturally occurring antibodies that attach to a key part of the parasite’s binding protein, preventing infection.
“The parasite protein is very large, and human antibodies bind to it at many different points along its length,” Dr Tolia explained. “We have observed that the ones that are most effective, so far, are the antibodies that bind to the protein at the region highlighted by our new research.” 
attached to syncytiotrophoblast
Credit: Fabio T.M. Costa
Plasmodium vivax malaria attacks red blood cells by clamping down on the cells with a pair of proteins, researchers have found.
Earlier studies suggested that a single P vivax protein binds to a protein on the surface of red blood cells.
But the new study showed that binding is a 2-step process that involves 2 copies of a parasite protein coming together like tongs around 2 copies of a host protein.
The researchers believe this discovery, detailed in PLOS Pathogens, could help scientists design better vaccines and treatments for P vivax, which is common in India, Southeast Asia, and South America.
“More people live at risk of infection by this strain of malaria than any other,” said senior study author Niraj Tolia, PhD, of the Washington University School of Medicine in St Louis, Missouri.
“We now are using what we have learned to create vaccines tailored to stop the infectious process by preventing the parasite from attaching to red blood cells.”
Dr Tolia and his colleagues knew that P vivax Duffy binding protein (DBP) recognizes the receptor Duffy antigen/receptor for chemokines (DARC) during the parasite’s invasion of red blood cells. But the team wanted to identify binding contacts during invasion and determine the molecular basis of DBP receptor recognition.
So they conducted structural studies on the minimal binding domain of DBP in complex with the minimal region from DARC. And they found that 2 DBP molecules bind 2 DARC molecules.
The researchers also performed erythrocyte binding assays with binding site mutants and identified essential receptor contacts.
“It’s a very intricate and chemically strong interaction that was not easily understood before,” Dr Tolia said. “We have had hints that other forms of malaria, including the African strain, may be binding in a similar fashion to host cells, but this is one of the first definitive proofs of this kind of attack.”
Dr Tolia suspects that blocking any of the proteins with drugs or vaccines will stop the infectious process.
“For example, some people have a mutation that eliminates the protein on red blood cell surfaces that P vivax binds to, and they tend to be resistant to the parasite,” he said. “This is why this strain isn’t prevalent in Africa. Evolutionary pressure has caused most of the populations there to stop making this protein.”
Dr Tolia and his colleagues also found evidence that other people with immunity to P vivax have developed naturally occurring antibodies that attach to a key part of the parasite’s binding protein, preventing infection.
“The parasite protein is very large, and human antibodies bind to it at many different points along its length,” Dr Tolia explained. “We have observed that the ones that are most effective, so far, are the antibodies that bind to the protein at the region highlighted by our new research.”
attached to syncytiotrophoblast
Credit: Fabio T.M. Costa
Plasmodium vivax malaria attacks red blood cells by clamping down on the cells with a pair of proteins, researchers have found.
Earlier studies suggested that a single P vivax protein binds to a protein on the surface of red blood cells.
But the new study showed that binding is a 2-step process that involves 2 copies of a parasite protein coming together like tongs around 2 copies of a host protein.
The researchers believe this discovery, detailed in PLOS Pathogens, could help scientists design better vaccines and treatments for P vivax, which is common in India, Southeast Asia, and South America.
“More people live at risk of infection by this strain of malaria than any other,” said senior study author Niraj Tolia, PhD, of the Washington University School of Medicine in St Louis, Missouri.
“We now are using what we have learned to create vaccines tailored to stop the infectious process by preventing the parasite from attaching to red blood cells.”
Dr Tolia and his colleagues knew that P vivax Duffy binding protein (DBP) recognizes the receptor Duffy antigen/receptor for chemokines (DARC) during the parasite’s invasion of red blood cells. But the team wanted to identify binding contacts during invasion and determine the molecular basis of DBP receptor recognition.
So they conducted structural studies on the minimal binding domain of DBP in complex with the minimal region from DARC. And they found that 2 DBP molecules bind 2 DARC molecules.
The researchers also performed erythrocyte binding assays with binding site mutants and identified essential receptor contacts.
“It’s a very intricate and chemically strong interaction that was not easily understood before,” Dr Tolia said. “We have had hints that other forms of malaria, including the African strain, may be binding in a similar fashion to host cells, but this is one of the first definitive proofs of this kind of attack.”
Dr Tolia suspects that blocking any of the proteins with drugs or vaccines will stop the infectious process.
“For example, some people have a mutation that eliminates the protein on red blood cell surfaces that P vivax binds to, and they tend to be resistant to the parasite,” he said. “This is why this strain isn’t prevalent in Africa. Evolutionary pressure has caused most of the populations there to stop making this protein.”
Dr Tolia and his colleagues also found evidence that other people with immunity to P vivax have developed naturally occurring antibodies that attach to a key part of the parasite’s binding protein, preventing infection.
“The parasite protein is very large, and human antibodies bind to it at many different points along its length,” Dr Tolia explained. “We have observed that the ones that are most effective, so far, are the antibodies that bind to the protein at the region highlighted by our new research.”