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Structural insights into MIC2 recognition by MIC2-associated protein in Toxoplasma gondii
Open accessPublished version of a preprint
Abstract
Microneme protein 2 (MIC2) and MIC2-associated protein (M2AP) play crucial roles in the gliding motility and host cell invasion of Toxoplasma gondii . Complex formation between MIC2 and M2AP is required for maturation and transport from the microneme to the parasite surface. Previous studies showed that M2AP associates with the 6 th TSR domain of MIC2 (TSR6), but the detailed interaction remains unclear. In this study, we report crystal structures of M2AP alone and in complex with TSR6. TSR domains have an unusually thin, long structure with a layer of intercalated residues on one side. The non-layered side of TSR6 with hotspot residue His-620 at the center binds to M2AP. Remarkably, we show that TSR6 residue Y602 is dynamic; it equilibrates between being part of the layer (the layered state) and in a flipped-out state in the absence of M2AP. However, when bound to M2AP, Y602 shifts to the flipped-out state. Our findings provide insights into the association and stabilization of MIC2-M2AP complex, and may be used to develop new therapies to prevent infections caused by this parasite.
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Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764
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Research works printed but not linked: 27
- Halonen, S. K. & Weiss, L. M. Toxoplasmosis. Handb. Clin. Neurol. 114, 125–145 (2013). · DOI
- Carruthers, V. B., Giddings, O. K. & Sibley, L. D. Secretion of micronemal proteins is associated with toxoplasma invasion of host cells. Cell Microbiol. 1, 225–235 (1999). · DOI
- Huynh, M. H. et al. Rapid invasion of host cells by Toxoplasma requires secretion of the MIC2-M2AP adhesive protein complex. EMBO J 22, 2082–2090 (2003). · DOI
- Huynh, M. H. & Carruthers, V. B. Toxoplasma MIC2 is a major determinant of invasion and virulence. PLoS Pathog. 2, e84 (2006). · DOI
- Jewett, T. J. & Sibley, L. D. Aldolase forms a bridge between cell surface adhesins and the actin cytoskeleton in apicomplexan parasites. Mol. Cell 11, 885–894 (2003). · DOI
- Rabenau, K. E. et al. TgM2AP participates in Toxoplasma gondii invasion of host cells and is tightly associated with the adhesive protein TgMIC2. Mol. Microbiol. 41, 537–547 (2001). · DOI
- Huynh, M. H. et al. Trans-genera reconstitution and complementation of an adhesion complex in Toxoplasma gondii. Cell Microbiol. 6, 771–782 (2004). · DOI
- Harper, J. M. et al. A cleavable propeptide influences Toxoplasma infection by facilitating the trafficking and secretion of the TgMIC2-M2AP invasion complex. Mol. Biol. Cell 17, 4551–4563 (2006). · DOI
- Song, G. & Springer, T. A. Structures of the Toxoplasma gliding motility adhesin. Proc. Natl. Acad. Sci. USA 111, 4862–4867 (2014). · DOI
- Springer, T. A. Complement and the multifaceted functions of VWA and integrin I domains. Structure 14, 1611–1616 (2006). · DOI
- Shimaoka, M., Takagi, J. & Springer, T. A. Conformational regulation of integrin structure and function. Annu. Rev. Biophys. Biomol. Struct. 31, 485–516 (2002). · DOI
- Song, G., Koksal, A. C., Lu, C. & Springer, T. A. Shape change in the receptor for gliding motility in Plasmodium sporozoites. Proc. Natl. Acad. Sci. USA 109, 21420–21425 (2012). · DOI
- Huynh, M. H. et al. Structural basis of Toxoplasma gondii MIC2-associated protein interaction with MIC2. J. Biol. Chem. 290, 1432–1441 (2015). · DOI
- Wang, X. et al. A genetically encoded F-19 NMR probe reveals the allosteric modulation mechanism of cannabinoid receptor 1. J. Am. Chem. Soc. 143, 16320–16325 (2021). · DOI
- Shi, P. et al. Site-specific protein backbone and side-chain NMR chemical shift and relaxation analysis of human vinexin SH3 domain using a genetically encoded 15N/19F-labeled unnatural amino acid. Biochem. Biophys. Res. Commun. 402, 461–466 (2010). · DOI
- Liu, D. & Wüthrich, K. Ring current shifts in (19)F-NMR of membrane proteins. J. Biomol. NMR 65, 1–5 (2016). · DOI
- Pääkkönen, K. et al. Solution structures of the first and fourth TSR domains of F-spondin. Proteins 64, 665–672 (2006). · DOI
- Tan, K. et al. Crystal structure of the TSP-1 type 1 repeats: a novel layered fold and its biological implication. J. Cell Biol. 159, 373–382 (2002). · DOI
- Niu, M. et al. Structural basis for CD97 recognition of the decay-accelerating factor CD55 suggests mechanosensitive activation of adhesion GPCRs. J. Biol. Chem. 296, 100776 (2021). · DOI
- Di Cristina, M., Spaccapelo, R., Soldati, D., Bistoni, F. & Crisanti, A. Two conserved amino acid motifs mediate protein targeting to the micronemes of the apicomplexan parasite Toxoplasma gondii. Mol. Cell. Biol. 20, 7332–7341 (2000). · DOI
- Kabsch, W. XDS. Acta Crystallogr. D Biol. Crystallogr. 66, 125–132 (2010). · DOI · Paper page
- Hunter, M. S. et al. Selenium single-wavelength anomalous diffraction de novo phasing using an X-ray-free electron laser. Nat. Commun. 7, 13388 (2016). · DOI
- Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D Biol. Crystallogr. 66, 213–221 (2010). · DOI · Paper page
- Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D Biol. Crystallogr. 66, 486–501 (2010). · DOI · Paper page
- Robert, X. & Gouet, P. Deciphering key features in protein structures with the new ENDscript server. Nucleic Acids Res. 42, W320–W324 (2014). · DOI · Paper page
- Hammill, J. T., Miyake-Stoner, S., Hazen, J. L., Jackson, J. C. & Mehl, R. A. Preparation of site-specifically labeled fluorinated proteins for 19F-NMR structural characterization. Nat. Protoc. 2, 2601–2607 (2007). · DOI
- Jackson, J. C., Hammill, J. T. & Mehl, R. A. Site-specific incorporation of a (19)F-amino acid into proteins as an NMR probe for characterizing protein structure and reactivity. J. Am. Chem. Soc. 129, 1160–1166 (2007). · DOI
Metadata
- Authors
- Zhang, S., Wang, F., Zhang, D., Liu, D., Ding, W., Springer, T. A., & Song, G.
- Affiliations
- East China Normal University (CN)
- ShanghaiTech University (CN)
- Chinese Academy of Sciences (CN)
- Boston Children's Hospital (US)
- Corresponding author
- Song, Gaojie
- Venue
- Communications Biology
- Published
- 2023-08-31
- Volume
- 6
- Issue
- 1
- Pages
- 895-895
- ISSN
- 2399-3642 (ISSN-L)
- PMC
- PMC10471735
- OpenAlex
- W4386326417
- Cited by
- 6
- References
- 1
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 2 · 2023: 1
- FWCI
- 1.41
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Communications Biology (publishedVersion, cc-by)
- Research Square (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (32171215)
- Topics
- Life Sciences › Immunology and Microbiology › Parasitology › Toxoplasma gondii Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
- Keywords
- Toxoplasma gondii, CD99, microneme proteins, protein-protein interaction, crystal structure, residue dynamics, gliding motility, host cell invasion
- MeSH terms
- Humans, Problem Solving, Research Personnel, Toxoplasma, Recognition, Psychology
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