Pathways & interactions
Alpha giardin (IPR008088)
Short name: Alpha_giardin
- Annexin (IPR001464)
- Alpha giardin (IPR008088)
The annexins (or lipocortins) are a family of proteins that bind to phospholipids in a calcium-dependent manner [PMID: 1646719]. They are distributed ubiquitously in different tissues and cell types of higher and lower eukaryotes, including mammals, fish, birds, Drosophila melanogaster (Fruit fly), Xenopus laevis (African clawed frog), Caenorhabditis elegans , Dictyostelium discoideum (Slime mold) and Neurospora crassa [PMID: 9797403, PMID: 9165068]. Annexins are absent from yeasts and prokaryotes [PMID: 15059252]. The plant annexins are somewhat distinct from those found in other taxa [PMID: 9165068].
Most eukaryotic species have 1-20 annexin (ANX) genes. All annexins share a core domain made up of four similar repeats, each approximately 70 amino acids long [PMID: 1646719]. Each individual annexin repeat (sometimes referred to as endonexin folds) is folded into five alpha-helices, and in turn are wound into a right-handed super-helix; they usually contain a characteristic 'type 2' motif for binding calcium ions with the sequence 'GxGT-[38 residues]-D/E'. Animal and fungal annexins also have variable amino-terminal domains. The core domains of most vertebrate annexins have been analysed by X-ray crystallography, revealing conservation of their secondary and tertiary structures despite only 45-55% amino-acid identity among individual members. The four repeats pack into a structure that resembles a flattened disc, with a slightly convex surface on which the Ca 2+ -binding loops are located and a concave surface at which the amino and carboxyl termini come into close apposition.
Annexins are traditionally thought of as calcium-dependent phospholipid-binding proteins, but recent work suggests a more complex set of functions. The famiy has been linked with inhibition of phospholipase activity, exocytosis and endoctyosis, signal transduction, organisation of the extracellular matrix, resistance to reactive oxygen species and DNA replication [PMID: 9797403].
Giardia lamblia (Giardia intestinalis) is a protozoan parasite of numerous mammals, including Homo sapiens [PMID: 11432808]. It belongs to the phylum Sarcomastigophora, and is amongst the most primitive eukaryotes identified to date. It is the main causative agent of global protozoan diarrhoea, and severe infection can cause giardiasis. G. lamblia exists as either trophozoites that live in the small intestine of the host and cause the disease symptoms, or cysts that are passed in the faeces of the host and infect the next host through contaminated water or food [PMID: 11432808].
Trophozoites exhibit antigenic variation to evade the host immune system, expressing a number of virulence factors to aid adherence and invasion of the small intestine endothelium [PMID: 7630843]. The molecular basis for its antigenic variation has been well characterised, and it is believed that its phenotypic heretogeneity arises from sexual reproduction [PMID: 7630843]. One of the major virulence factors of G. lamblia is giardin, an antigen expressed as several variants on the trophozoite surface [PMID: 8278341]. Alpha giardin is the predominant immunotypic giardin present, although beta and gamma giardin have also been identified [PMID: 8278341].
A recent study on the biochemical properties of alpha giardin has identified the protein as an annexin, a eukaryotic protein widely conserved amongst plants and animals. Purified alpha giardin associates with multimellar phosphatidyl serine-containing vesicles in a Ca2+-dependent manner, and has very low sequence similarity with human annexin XIX [PMID: 10220891].
- PR01712 (ALPHAGIARDIN)