title: Domains of invasion organelle proteins from apicomplexan parasites are homologous with the Apple domains of blood coagulation factor XI and plasma pre-kallikrein and are members of the PAN module superfamily.
abstract: Micronemes are specialised organelles, found in all apicomplexan parasites, which secrete molecules that are essential for parasite attachment to and invasion of host cells. Regions of several microneme proteins have sequence similarity to the Apple domains (A-domains) of blood coagulation factor XI (FXI) and plasma pre-kallikrein (PK). We have used mass spectrometry on a recombinant-expressed, putative A-domain from the microneme protein EtMIC5 from Eimeria tenella, to demonstrate that three intramolecular disulphide bridges are formed. These bridges are analogous to those that stabilise A-domains in FXI and PK. The data confirm that the apicomplexan domains are structural homologues of A-domains and are therefore novel members of the PAN module superfamily, which also includes the N-terminal domains of members of the plasminogen/hepatocyte growth factor family. The role of A-domains/PAN modules in apicomplexan parasites is not known, but their presence in the microneme suggests that they may be important for mediating protein-protein or protein-carbohydrate interactions during parasite attachment and host cell invasion.
authors.affiliation: Institute for Animal Health, Compton Laboratory, Compton, Newbury, Berkshire RG20 7NN, UK.
authors.forename: P J
authors.initials: PJ
authors.lastname: Brown
authors.forename: A C
authors.initials: AC
authors.lastname: Gill
authors.forename: P G
authors.initials: PG
authors.lastname: Nugent
authors.forename: J H
authors.initials: JH
authors.lastname: McVey
authors.forename: F M
authors.initials: FM
authors.lastname: Tomley
mesh_terms: D020816:Amino Acid Motifs / Q000502:physiology; D000818:Animals; D016782:Apicomplexa / Q000502:physiology*; D017124:Conserved Sequence; D004220:Disulfides / Q000737:chemistry; D016786:Eimeria tenella; D005172:Factor XI / Q000737:chemistry*; D008401:Gas Chromatography-Mass Spectrometry; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006790:Host-Parasite Interactions / Q000502:physiology; D005810:Multigene Family; D015388:Organelles / Q000378:metabolism*; D010446:Peptide Fragments / Q000032:analysis; D011288:Prekallikrein / Q000737:chemistry*; D017434:Protein Structure, Tertiary / Q000502:physiology; D015800:Protozoan Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D004220:Disulfides; D006023:Glycoproteins; D010446:Peptide Fragments; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; C408742:microneme protein 5, Eimeria tenella; D005172:Factor XI; D011288:Prekallikrein