Xia Xu, Du Chenqiang, Wang Yang, Song Gaojie
Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
Wenzhou Key Laboratory of Biomedical Imaging, Center of Biomedical Physics, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, China.
Proteins. 2025 Mar;93(3):620-628. doi: 10.1002/prot.26758. Epub 2024 Oct 22.
Microneme protein 2 (MIC2) and its associated protein M2AP are pivotal for the gliding motility and host cell invasion by Toxoplasma gondii. In our prior work, we showed that M2AP binds specifically to the sixth TSR domain of MIC2, with this interaction mediated dominantly by the hotspot residue H620 situated at the center of TSR6. To delve deeper into the functional significance of H620 and explore the dynamic behavior of Y602, we conducted molecular dynamic (MD) simulations of the Toxoplasma TSR6-M2AP complex, encompassing both wild-type and mutant forms. Our findings underscore the critical role of H620 within TSR6, particularly its hydrogen bond interaction with K72 of M2AP. The H620A mutation disrupts the nearby hydrophobic network while minimally affecting other hydrophilic interactions. Furthermore, our data reveal a highly conserved binding pose between M2AP and TSR6 across different species, consistent with previous trans-genera studies, thereby offering insights for future strategies in infection control development.
