PNAS: Find proteins that act directly on human cells and malaria

For the first time, scientists have revealed a doubt about malaria infection, which has uncovered a long-standing mystery. A protein called TRAP on the surface of a malaria pathogen is a highly valued therapeutic target, but how it interacts with human host cells remains a secret. Scientists from the Wellcome Sanger Institute have discovered that a receptor on the surface of human cells can interact with TRAP to direct it to move within the body.

The findings, published recently on PNAS, will help develop effective malaria vaccines.

Almost half of the world's population is at risk of malaria, with more than 200 million people infected with malaria every year. In 2015, the disease caused about 500,000 deaths.

Malaria is caused by the pathogen Plasmodium and can be transmitted by infected mosquito bites. Once the pathogens enter the human skin from the mosquitoes, they must migrate from the entry site into the next stage where the blood vessels eventually interact with the liver into life. However, molecular clues to the interaction of pathogens with human cells are unclear, making it difficult for scientists to intervene and prevent the migration of pathogens.

In this study, researchers first discovered that the pathogen surface protein TRAP directly interacts with a class of proteins called integrins on the surface of human cells.

Dr. Kirsten Dundas, the first author of the study, said: "This is the first human cell receptor to discover TRAP, a high-priority malaria vaccine target. The TRAP protein on the surface of malaria pathogens has been studied for nearly 20 years, but a major The question that does not find the answer is how it interacts with human cells. Disrupting this interaction is a key strategy to inhibit the migration of pathogens from the skin into the body."

The researchers dissected the infected mosquitoes and extracted the malaria pathogens at the stage of transmission (spore bodies). After the infected mosquito bites the human body, the spore body is transmitted to humans. This small body then navigates into the blood vessels of the human body and follows the blood vessels into the liver, infecting the liver cells and entering the next stage of life.

To study the receptors on the surface of human cells interacting with spores in the human circulation, the team interacted with a series of proteins on the surface of hepatocytes, using a technique called AVIES to detect proteins and cell surface proteins. interaction. The results show that the pathogen's TRAP interacts with human alpha-v-beta-3 integrin. It is likely that this integrin acts as a marker to direct pathogens into the liver cells.

Dr. Gavin Wright, the lead author of the study, said: "We have discovered a human receptor for TRAP that provides an example of a sporophytic surface protein that interacts directly with human cell surface receptors. This provides important clues that can guide We further look for molecules that direct pathogen localization and invade the human liver." (Sina Medical News)

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