The structure of a major surface antigen SAG19 from Eimeria tenella unifies the Eimeria SAG family

Abstract

In infections by apicomplexan parasites including Plasmodium, Toxoplasma gondii, and Eimeria, host interactions are mediated by proteins including families of membrane-anchored cysteine-rich surface antigens (SAGs) and SAG-related sequences (SRS). Eimeria tenella causes caecal coccidiosis in chickens and has a SAG family with over 80 members making up 1% of the proteome. We have solved the structure of a representative E. tenella SAG, EtSAG19, revealing that, despite a low level of sequence similarity, the entire Eimeria SAG family is unified by its three-layer αβα fold which is related to that of the CAP superfamily. Furthermore, sequence comparisons show that the Eimeria SAG fold is conserved in surface antigens of the human coccidial parasite Cyclospora cayetanensis but this fold is unrelated to that of the SAGs/SRS proteins expressed in other apicomplexans including Plasmodium species and the cyst-forming coccidia Toxoplasma gondii, Neospora caninum and Besnoitia besnoiti. However, despite having very different structures, Consurf analysis showed that Eimeria SAG and Toxoplasma SRS families each exhibit marked hotspots of sequence hypervariability that map to their surfaces distal to the membrane anchor. This suggests that the primary and convergent purpose of the different structures is to provide a platform onto which sequence variability can be imposed.

Dynamically expressed genes provide candidate viability biomarkers in a model coccidian

“…SAGs in Eimeria are different than the predominant surface antigens families in the apicomplexans Toxoplasma and Plasmodium [12]. Also, a recent study showed that a fold within a representative SAG B subfamily protein in E. tenella are distinct from surface antigens of Toxoplasma and Plasmodium, and that this fold defines other Eimeria SAG sub-families [118]. Furthermore, this fold is conserved in Eimeria and C. cayetanensis and unrelated to SAGs or SRS proteins in other cyst-forming coccidia.…”

GrAfSS: a webserver for substructure similarity searching and comparisons in the structures of proteins and RNA

“…One recent analysis that utilized the ASSAM server for substructure searching in such a way was the discovery of a four aspartates arrangement (4D motif) that is involved in binding a divalent metal ion to stabilize the acetylcholinesterase of Torpedo californica ( 30 ). Another example had used ASSAM to identify a 3D motif that could be regarded as a fingerprint for the fold of a protein superfamily ( 31 ).…”

Eimeria proteins: order amidst disorder

“…Genome annotation has revealed that pathogenic eimerian can have up to 105 sags and species with severe pathologies may have a higher number [ 46 ]. Over 80 sags have been identified to constitute about 1% of E. tenella proteome [ 59 ]. However, heterogeneity or nucleotide diversity of protein genes could vary in different isolates [ 60 ].…”

“…Currently, Emerian merozoites have about 47 SAGs whereas only 4 SAGs have been reported in the sporozoite of E. tenella [71] (Table 1). Eimeria tenella merozoite SAG, SAG 2, 4 and 19 are localised by a phospholipid anchor on the parasite surface membrane with variations in immunogenicity and abundance [59,111]. Nevertheless, Eimeria SAGs have significant homology with conserved surface antigens of C. cayetanensis [59].…”