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Published on: August 5, 2021
Structural Features of Apicomplexan Pore-Forming Proteins and Their Roles in Parasite Cell Traversal and Egress
Alfredo J Guerra1, Vern B Carruthers2
1Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109-5620, USA. galfredo@umich.edu.
Abstract:
Apicomplexan parasites cause diseases, including malaria and toxoplasmosis, in a range of hosts, including humans. These intracellular parasites utilize pore-forming proteins that disrupt host cell membranes to either traverse host cells while migrating through tissues or egress from the parasite-containing vacuole after replication. This review highlights recent insight gained from the newly available three-dimensional structures of several known or putative apicomplexan pore-forming proteins that contribute to cell traversal or egress. These new structural advances suggest that parasite pore-forming proteins use distinct mechanisms to disrupt host cell membranes at multiple steps in parasite life cycles. How proteolytic processing, secretion, environment, and the accessibility of lipid receptors regulate the membranolytic activities of such proteins is also discussed.
Insights
Apicomplexan parasites use pore-forming proteins to invade host cells and cause diseases like malaria. New 3D structures reveal distinct mechanisms these parasite proteins use to disrupt host cell membranes during infection.
Area of Science:
- Parasitology
- Structural Biology
- Molecular Biology
Background:
- Apicomplexan parasites cause significant human diseases such as malaria and toxoplasmosis.
- These parasites are intracellular and rely on specific proteins to breach host cell membranes for invasion, migration, and egress.
- Understanding these mechanisms is crucial for developing effective anti-parasitic therapies.
Purpose of the Study:
- To review recent advancements in understanding apicomplexan pore-forming proteins.
- To highlight insights gained from new three-dimensional structures of these proteins.
- To discuss the distinct mechanisms these proteins employ for host cell membrane disruption.
Main Methods:
- Review of recent scientific literature.
- Analysis of newly available three-dimensional structural data of apicomplexan pore-forming proteins.
- Discussion of functional and regulatory aspects of protein activity.
Main Results:
- New 3D structures illuminate distinct mechanisms of host cell membrane disruption by apicomplexan pore-forming proteins.
- These proteins are essential for parasite cell traversal and egress.
- Structural insights suggest varied strategies for membrane attack at different parasite life stages.
Conclusions:
- Apicomplexan pore-forming proteins exhibit diverse structural and functional mechanisms for host cell membrane disruption.
- Proteolytic processing, secretion, and lipid receptor accessibility are key regulators of their membranolytic activity.
- Further structural and functional studies will aid in targeting these essential parasite proteins.
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