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red blood cell; Credit: St Jude
Children’s Research Hospital
Two groups of researchers have found they can kill the malaria parasite by targeting a protein complex.
The research showed that a protein complex known as the Plasmodium translocon of exported proteins (PTEX) is needed for the export of malaria-parasite proteins into the cytoplasm of infected red blood cells, and such export is essential for parasite survival.
When the researchers disrupted passage of the proteins in cell cultures, malaria parasites stopped growing and died.
“The malaria parasite secretes hundreds of diverse proteins to seize control of red blood cells,” said Josh R. Beck, PhD, of the Washington University School of Medicine in St Louis.
“We’ve been searching for a single step that all those various proteins have to take to be secreted, and this looks like just such a bottleneck.”
He and his colleagues detailed their findings in a letter to Nature.
The researchers focused on heat shock protein 101 (HSP101), a component of PTEX. Previous studies had suggested that HSP101 might be involved in protein secretion.
So Dr Beck and his colleagues disabled HSP101 in cell cultures, expecting to block the discharge of some malarial proteins. To their surprise, they stopped all of them.
“We think this is a very promising target for drug development,” said study author Daniel Goldberg, MD, PhD, also of Washington University.
“We’re a long way from getting a new drug, but, in the short term, we may look at screening a variety of compounds to see if they have the potential to block HSP101.”
The researchers think HSP101 may ready malarial proteins for secretion through a pore that opens into the red blood cell. Part of this preparation may involve unfolding the proteins into a linear form that allows them to more easily pass through the pore. HSP101 may also give the proteins a biochemical kick that pushes them through the pore.
A separate study published in the same issue of Nature also highlights the importance of PTEX to the malaria parasite’s survival.
Brendan Elsworth, of the Macfarlane Burnet Institute for Medical Research and Public Health in Melbourne, Australia, and his colleagues neutralized the malaria parasite by disabling either HSP101 or PTEX150, another component of PTEX.
“That suggests there are multiple components of the process that we may be able to target with drugs,” Dr Beck said. “In addition, many of the proteins involved in secretion are unlike any human proteins, which means we may be able to disable them without adversely affecting important human proteins.” 
red blood cell; Credit: St Jude
Children’s Research Hospital
Two groups of researchers have found they can kill the malaria parasite by targeting a protein complex.
The research showed that a protein complex known as the Plasmodium translocon of exported proteins (PTEX) is needed for the export of malaria-parasite proteins into the cytoplasm of infected red blood cells, and such export is essential for parasite survival.
When the researchers disrupted passage of the proteins in cell cultures, malaria parasites stopped growing and died.
“The malaria parasite secretes hundreds of diverse proteins to seize control of red blood cells,” said Josh R. Beck, PhD, of the Washington University School of Medicine in St Louis.
“We’ve been searching for a single step that all those various proteins have to take to be secreted, and this looks like just such a bottleneck.”
He and his colleagues detailed their findings in a letter to Nature.
The researchers focused on heat shock protein 101 (HSP101), a component of PTEX. Previous studies had suggested that HSP101 might be involved in protein secretion.
So Dr Beck and his colleagues disabled HSP101 in cell cultures, expecting to block the discharge of some malarial proteins. To their surprise, they stopped all of them.
“We think this is a very promising target for drug development,” said study author Daniel Goldberg, MD, PhD, also of Washington University.
“We’re a long way from getting a new drug, but, in the short term, we may look at screening a variety of compounds to see if they have the potential to block HSP101.”
The researchers think HSP101 may ready malarial proteins for secretion through a pore that opens into the red blood cell. Part of this preparation may involve unfolding the proteins into a linear form that allows them to more easily pass through the pore. HSP101 may also give the proteins a biochemical kick that pushes them through the pore.
A separate study published in the same issue of Nature also highlights the importance of PTEX to the malaria parasite’s survival.
Brendan Elsworth, of the Macfarlane Burnet Institute for Medical Research and Public Health in Melbourne, Australia, and his colleagues neutralized the malaria parasite by disabling either HSP101 or PTEX150, another component of PTEX.
“That suggests there are multiple components of the process that we may be able to target with drugs,” Dr Beck said. “In addition, many of the proteins involved in secretion are unlike any human proteins, which means we may be able to disable them without adversely affecting important human proteins.”
red blood cell; Credit: St Jude
Children’s Research Hospital
Two groups of researchers have found they can kill the malaria parasite by targeting a protein complex.
The research showed that a protein complex known as the Plasmodium translocon of exported proteins (PTEX) is needed for the export of malaria-parasite proteins into the cytoplasm of infected red blood cells, and such export is essential for parasite survival.
When the researchers disrupted passage of the proteins in cell cultures, malaria parasites stopped growing and died.
“The malaria parasite secretes hundreds of diverse proteins to seize control of red blood cells,” said Josh R. Beck, PhD, of the Washington University School of Medicine in St Louis.
“We’ve been searching for a single step that all those various proteins have to take to be secreted, and this looks like just such a bottleneck.”
He and his colleagues detailed their findings in a letter to Nature.
The researchers focused on heat shock protein 101 (HSP101), a component of PTEX. Previous studies had suggested that HSP101 might be involved in protein secretion.
So Dr Beck and his colleagues disabled HSP101 in cell cultures, expecting to block the discharge of some malarial proteins. To their surprise, they stopped all of them.
“We think this is a very promising target for drug development,” said study author Daniel Goldberg, MD, PhD, also of Washington University.
“We’re a long way from getting a new drug, but, in the short term, we may look at screening a variety of compounds to see if they have the potential to block HSP101.”
The researchers think HSP101 may ready malarial proteins for secretion through a pore that opens into the red blood cell. Part of this preparation may involve unfolding the proteins into a linear form that allows them to more easily pass through the pore. HSP101 may also give the proteins a biochemical kick that pushes them through the pore.
A separate study published in the same issue of Nature also highlights the importance of PTEX to the malaria parasite’s survival.
Brendan Elsworth, of the Macfarlane Burnet Institute for Medical Research and Public Health in Melbourne, Australia, and his colleagues neutralized the malaria parasite by disabling either HSP101 or PTEX150, another component of PTEX.
“That suggests there are multiple components of the process that we may be able to target with drugs,” Dr Beck said. “In addition, many of the proteins involved in secretion are unlike any human proteins, which means we may be able to disable them without adversely affecting important human proteins.”