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infecting a red blood cell
Image courtesy of St. Jude
Children’s Research Hospital
Researchers have reconstructed how malaria parasite proteins bind to the antibodies that act as the first line of defense against the parasite.
The team described the binding of immunoglobulin M (IgM) to Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP1).
They said their findings, published in Cell Reports, may provide valuable knowledge for the design of antimalarial drugs.
One strategy the malaria parasite Plasmodium falciparum uses to amplify its probability of spreading is the formation of rosette-shaped clusters of uninfected red blood cells (RBCs) surrounding a malaria-infected RBC.
Since the parasite in the central cell of the rosette can easily infect the surrounding cells, the rosette enhances the infection. Rosetting is associated with severe malaria and high fever.
One of the key players in the formation of the rosette is PfEMP1. PfEMP1 sticks out of the infected RBC and deceives one of the first defenses against malaria—IgM antibodies.
IgMs bind to the parasite or parasite-infected cells and call other immune molecules, like the complement system, for backup.
With the current study, researchers have shown that IgMs bind 1 or 2 PfEMP1 proteins, forming a bouquet-type shape on the surface of the infected cells.
Plasmodium falciparum exploits these IgMs to its own advantage because the bouquet attracts more RBCs, facilitating the formation of rosettes. Moreover, the IgMs in the bouquet are not able to bind the complement system and destroy the infected cell.
“The bond between PfEMP1s and IgMs is like the perfect Velcro—not too loose, not too strong,” said Ulf Skoglund, PhD, of Okinawa Institute for Science and Technology Graduate University in Japan.
“It is devilishly engineered to fool our immune system.”
The technique Dr Skoglund and his colleagues used to assess this bond allowed them to have a unique view of the proteins’ conformation.
“We have seen that PfEMP1 is a stiff, C-shaped protein,” he said. “Being stiff is an advantage. If it was floppy, it would not work so well. IgM, instead, assume 3 conformations: extended, bell, and turtle shape.”
Dr Skoglund and his colleagues believe that having this 3D structural model of the PfEMP1 and IgM complex can help scientists design antimalarial treatments that can break down or wash out malaria rosettes without hurting the patient. 
infecting a red blood cell
Image courtesy of St. Jude
Children’s Research Hospital
Researchers have reconstructed how malaria parasite proteins bind to the antibodies that act as the first line of defense against the parasite.
The team described the binding of immunoglobulin M (IgM) to Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP1).
They said their findings, published in Cell Reports, may provide valuable knowledge for the design of antimalarial drugs.
One strategy the malaria parasite Plasmodium falciparum uses to amplify its probability of spreading is the formation of rosette-shaped clusters of uninfected red blood cells (RBCs) surrounding a malaria-infected RBC.
Since the parasite in the central cell of the rosette can easily infect the surrounding cells, the rosette enhances the infection. Rosetting is associated with severe malaria and high fever.
One of the key players in the formation of the rosette is PfEMP1. PfEMP1 sticks out of the infected RBC and deceives one of the first defenses against malaria—IgM antibodies.
IgMs bind to the parasite or parasite-infected cells and call other immune molecules, like the complement system, for backup.
With the current study, researchers have shown that IgMs bind 1 or 2 PfEMP1 proteins, forming a bouquet-type shape on the surface of the infected cells.
Plasmodium falciparum exploits these IgMs to its own advantage because the bouquet attracts more RBCs, facilitating the formation of rosettes. Moreover, the IgMs in the bouquet are not able to bind the complement system and destroy the infected cell.
“The bond between PfEMP1s and IgMs is like the perfect Velcro—not too loose, not too strong,” said Ulf Skoglund, PhD, of Okinawa Institute for Science and Technology Graduate University in Japan.
“It is devilishly engineered to fool our immune system.”
The technique Dr Skoglund and his colleagues used to assess this bond allowed them to have a unique view of the proteins’ conformation.
“We have seen that PfEMP1 is a stiff, C-shaped protein,” he said. “Being stiff is an advantage. If it was floppy, it would not work so well. IgM, instead, assume 3 conformations: extended, bell, and turtle shape.”
Dr Skoglund and his colleagues believe that having this 3D structural model of the PfEMP1 and IgM complex can help scientists design antimalarial treatments that can break down or wash out malaria rosettes without hurting the patient.
infecting a red blood cell
Image courtesy of St. Jude
Children’s Research Hospital
Researchers have reconstructed how malaria parasite proteins bind to the antibodies that act as the first line of defense against the parasite.
The team described the binding of immunoglobulin M (IgM) to Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP1).
They said their findings, published in Cell Reports, may provide valuable knowledge for the design of antimalarial drugs.
One strategy the malaria parasite Plasmodium falciparum uses to amplify its probability of spreading is the formation of rosette-shaped clusters of uninfected red blood cells (RBCs) surrounding a malaria-infected RBC.
Since the parasite in the central cell of the rosette can easily infect the surrounding cells, the rosette enhances the infection. Rosetting is associated with severe malaria and high fever.
One of the key players in the formation of the rosette is PfEMP1. PfEMP1 sticks out of the infected RBC and deceives one of the first defenses against malaria—IgM antibodies.
IgMs bind to the parasite or parasite-infected cells and call other immune molecules, like the complement system, for backup.
With the current study, researchers have shown that IgMs bind 1 or 2 PfEMP1 proteins, forming a bouquet-type shape on the surface of the infected cells.
Plasmodium falciparum exploits these IgMs to its own advantage because the bouquet attracts more RBCs, facilitating the formation of rosettes. Moreover, the IgMs in the bouquet are not able to bind the complement system and destroy the infected cell.
“The bond between PfEMP1s and IgMs is like the perfect Velcro—not too loose, not too strong,” said Ulf Skoglund, PhD, of Okinawa Institute for Science and Technology Graduate University in Japan.
“It is devilishly engineered to fool our immune system.”
The technique Dr Skoglund and his colleagues used to assess this bond allowed them to have a unique view of the proteins’ conformation.
“We have seen that PfEMP1 is a stiff, C-shaped protein,” he said. “Being stiff is an advantage. If it was floppy, it would not work so well. IgM, instead, assume 3 conformations: extended, bell, and turtle shape.”
Dr Skoglund and his colleagues believe that having this 3D structural model of the PfEMP1 and IgM complex can help scientists design antimalarial treatments that can break down or wash out malaria rosettes without hurting the patient.