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

Ramly, Nur Zazarina; Dix, Samuel R.; Ruzheinikov, Sergey N.; Sedelnikova, Svetlana E.; Baker, Patrick J.; Chow, Yock-Ping; Tomley, Fiona M.; Blake, Damer P.; Wan, Kiew-Lian; Nathan, Sheila; Rice, David W.

Abstract

In infections by apicomplexan parasites including Plasmodium, Toxoplasma gondii, and Eimeria, interactions with the host are mediated by numerous 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 that encompasses over 80 members that make up 1% of the proteome. We have solved and analysed the structure of a representative E. tenella SAG, EtSAG19, to reveal that despite a very 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 cayetensis 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 exclusively to their surfaces distal to the membrane anchor. This suggests that the primary and convergent purpose of the two different structures is to provide a stable platform onto which sequence variability can be imposed.

Citation

Ramly, N. Z., Dix, S. R., Ruzheinikov, S. N., Sedelnikova, S. E., Baker, P. J., Chow, Y., …Rice, D. W. (2021). The structure of a major surface antigen SAG19 from Eimeria tenella unifies the Eimeria SAG family. Communications Biology, 4(1), https://doi.org/10.1038/s42003-021-01904-w

• Journal Article Type: Article
• Acceptance Date: Feb 19, 2021
• Online Publication Date: Mar 19, 2021
• Publication Date: 2021-12
• Deposit Date: Mar 25, 2021
• Publicly Available Date: Apr 13, 2021
• Journal: Communications Biology
• Publisher: Nature Research
• Peer Reviewed: Peer Reviewed
• Volume: 4
• Issue: 1
• Article Number: 376
• DOI: https://doi.org/10.1038/s42003-021-01904-w
• Public URL: https://rvc-repository.worktribe.com/output/1547974
• Publisher URL: https://www.nature.com/articles/s42003-021-01904-w
• Additional Information: Received: 27 August 2020; Accepted: 19 February 2021; First Online: 19 March 2021; : The authors declare no competing interests.