Apicomplexan perforin-like proteins

Björn F C Kafsack1, Vern B Carruthers

  • 1Department of Microbiology and Immunology; University of Michigan; Ann Arbor, MI USA.

Insights

Apicomplexan parasites utilize perforin-like proteins (ApiPLPs) with MACPF domains for membrane attack. These proteins are crucial for parasite pathogenesis, egress, and cell traversal.

Area of Science:

  • Parasitology
  • Structural Biology
  • Genomics

Background:

  • Apicomplexan parasites encode numerous perforin-like proteins (ApiPLPs) vital for pathogenesis and lifecycle progression.
  • These ApiPLPs feature a MACPF domain, known for pore formation in target membranes.
  • ApiPLP MACPF domains, while retaining key structural elements, exhibit novel domain arrangements.

Purpose of the Study:

  • To provide a comprehensive overview of the ApiPLP protein family.
  • To examine ApiPLPs from structural, functional, and phylogenetic perspectives across Apicomplexa.
  • To highlight the role of ApiPLPs in parasite-host interactions and pathogenesis.

Main Methods:

  • Comparative genomics analysis of ApiPLP genes across various apicomplexan species.
  • Structural analysis of MACPF domains and associated domains in ApiPLPs.
  • Phylogenetic reconstruction to understand the evolutionary relationships of ApiPLPs.
  • Literature review of functional studies on ApiPLPs in key apicomplexan models like Toxoplasma and Plasmodium.

Main Results:

  • ApiPLPs are widespread in Apicomplexa, with diverse domain architectures.
  • The MACPF domain is conserved, suggesting a conserved pore-forming function.
  • ApiPLPs are implicated in essential processes such as host cell invasion and parasite egress.
  • Structural variations in ApiPLPs may confer specialized functions in different parasite species.

Conclusions:

  • ApiPLPs represent a critical protein family in Apicomplexa, essential for parasite survival and virulence.
  • Understanding the structure-function relationships of ApiPLPs can reveal novel therapeutic targets.
  • Further research into ApiPLP diversity and function will enhance our knowledge of apicomplexan biology.

Related Concept Videos

Diversity of Protists II01:27

Diversity of Protists II

Alveolates are a group of organisms recognized by the presence of alveoli, which are cytoplasmic sacs located beneath the cell membrane. While their function remains uncertain, alveoli may help regulate water balance by controlling how much water enters and leaves the cell. In dinoflagellates, these structures may serve as armor plates. There are three major types of alveolates: ciliates, which move using cilia; dinoflagellates, which use flagella for movement; and apicomplexans, which are...
Antimicrobial Proteins01:23

Antimicrobial Proteins

Antimicrobial proteins are important components of the immune system. They aid the body in combating pathogens by either killing them directly or hindering their replication processes. Four main types of antimicrobial substances are interferons, the complement system, iron-binding proteins, and antimicrobial proteins.
Interferons
Interferons (IFNs) are proteins produced by lymphocytes, macrophages, and fibroblasts infected with viruses. While IFNs cannot prevent viruses from entering and...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However, invadopodia can...
Structure of Porins01:21

Structure of Porins

Mitochondria, chloroplasts, and gram-negative bacteria have transmembrane, beta-barrel proteins called porins to mediate the free diffusion of ions and metabolites across the membrane. Mitochondrial porin precursors contain conserved amino acid sequences called beta signals at their C-terminal. Beta signals have a  motif of PoXGXXHyXHy (Po-Polar, X-Any amino acid, G-Glycine, Hy-LargeHydrophobic), which are crucial for precursor recognition to initiate precursor assembly. Beta-barrel precursors...
Mechanism of Filopodia Formation01:39

Mechanism of Filopodia Formation

Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...