Microneme proteins in apicomplexans

Abstract

Microneme secretion supports several key cellular processes including gliding motility, active cell invasion and migration through cells, biological barriers, and tissues. The modular design of microneme proteins enables these molecules to assist each other in folding and passage through the quality control system, accurately target to the micronemes, oligimerizing with other parasite proteins, and engaging a variety of host receptors for migration and cell invasion. Structural and biochemical analyses of MIC domains is providing new perspectives on how adhesion is regulated and the potentially distinct roles MICs might play in long or short range interactions during parasite attachment and entry. New access to complete genome sequences and ongoing advances in genetic manipulation should provide fertile ground for refining current models and defining exciting new roles for MICs in apicomplexan biology.

Figure 1

Modular MICs. Schematic representations of known microneme proteins from four different apicomplexan genera are depicted (not to scale). Accession numbers, where available: Eimeria tenella MIC1, M73495; EtMIC2, Z71755; EtMIC3, AAR87667; EtMIC4, CAC34726; EtMIC5, AJ245536; Cryptosporidium parvum TRAP-C1, AAB92609; GP900, AAC98153; CpSCRP AF061328; Plasmodium falciparum TRAP, AAC1867; Plasmodium berghei SPECT, BAD08209; PbSPECT2, BAD83404; PbCelTOS, BAD97683; PbSOAP, AAL07530; PbCHT1, CAC40151; PbWARP, AAK83296; PbMOAP, AAV28504; PbCTRP, AAF73158; Toxoplasma gondii MIC1, CAA96466; TgMIC2, AAB63303; TgM2AP, AAK74070; TgMIC3, CAB56644; TgMIC4 AAD33906; TgMIC5, CAA70921; TgMIC6, AAD28185; TgMIC7, AAK35070; TgMIC8, AAK19757; TgMIC9, AAK19758; TgMIC10, AAG32024; TgMIC11, AAN16379; TgMIC12, AAK58479; TgAMA1, AF010264; TgSUB1, AAK94670.

Figure 2

Structural features of micronemal ligands. (A) MICs from Eimeria (EtMIC4-MIC5), Toxoplasma (TgMIC1-4-6, TgMIC2-M2AP) and Plasmodium (PvAMA1) are schematically depicted with a scale (left) illustrating the approximate distance they would project from the parasite membrane, assuming a fully elongated state. Projection estimates are based on the dimensions of the domain types shown as ribbon structures, with α-helices (red), β-sheets (blue), and random coils or turns (grey). Structures are based on the following: cbEGF from fibrillin (Protein Data Bank accession number 1EMO), PAN/Apple from EtMIC5 (1HKY), A/I domain from integrin α_L (1MQA), TSR from thrombospondin (1LSL), ectodomain of PvAMA1 (1W8K). (B) Model based on of an integrin heterodimer in the closed (low affinity) and the open (high affinity) configuration.