Molecular Mimicry by Toxoplasma gondii B-Cell Epitopes of Neurodevelopmental Proteins: An Immunoinformatic Approach
Abstract
:1. Introduction
2. Materials and Methods
2.1. T. gondii Epitope Prediction
2.2. List of Human Surface Proteins Involved in Brain Development and Differentiation
2.3. Similarity between T. gondii Epitopes and Human Surface Proteins Involved in Brain Development
2.4. Similarity between T. gondii Epitopes and Human Surface Proteins Not Involved in Brain Development
2.5. Protein Network of Human Proteins with the Potential for Molecular Mimicry
2.6. Expression of Genes Identified as Potential Targets of Molecular Mimicry in Mouse Development
2.7. Prediction of Protein Topology
2.8. Overlapping of Protein Structures
3. Results
3.1. Prediction of T. gondii B-Cell Epitopes
3.2. Prediction of Human Proteins with Potential for Molecular Mimicry by T. gondii B-Cell Epitopes
3.3. Network Prediction of Human Proteins with the Potential for Molecular Mimicry
3.4. Expression Profiles of the Genes with the Potential for Molecular Mimicry during Development
3.5. Structural Overlap in Extracellular Regions
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Alignment Positions | Extracellular Region Positions | |||||
---|---|---|---|---|---|---|
Protein Name | Start (aa) | End (aa) | Alignment Length | e-Value | Start (aa) | End (aa) |
ANK3 | 363 | 527 | 168 | 9.09 × 10−16 | φ | φ |
BMPR1A | 240 | 529 | 321 | 6.20 × 10−11 | 24 | 153 |
BMPR2 | 206 | 534 | 354 | 3.78 × 10−7 | 27 | 149 |
CSF1R | 704 | 908 | 213 | 3.48 × 10−9 | 22 | 515 |
EPHA2 | 615 | 870 | 264 | 3.01 × 10−17 | 24 | 535 |
EPHA4 | 622 | 876 | 263 | 6.30 × 10−15 | 22 | 547 |
EPHA5 | 694 | 971 | 327 | 3.75 × 10−13 | 22 | 573 |
EPHB2 | 625 | 877 | 261 | 6.40 × 10−17 | 22 | 544 |
FGFR2 | 399 | 666 | 272 | 3.64 × 10−14 | 23 | 377 |
HMGB1 | 83 | 165 | 85 | 2.70 × 10−12 | φ | φ |
HSP90AA1 | 18 | 703 | 721 | 0.0 | φ | φ |
HSP90AB1 | 17 | 717 | 739 | 0.0 | φ | φ |
LYN | 248 | 508 | 284 | 2.65 × 10−8 | φ | φ |
NOTCH1 receptor | 707 | 944 | 283 | 1.28 × 10−4 | 22 | 1735 |
NOTCH2 receptor | 651 | 922 | 281 | 6.31 × 10−8 | 26 | 1677 |
NOTCH3 receptor | 1079 | 1373 | 295 | 7.30 × 10−7 | 22 | 1643 |
NRDC | 205 | 1089 | 916 | 2.52 × 10−65 | φ | φ |
NTRK1 | 509 | 777 | 273 | 6.65 × 10−11 | 31 | 417 |
ROR1 | 476 | 736 | 262 | 9.72 × 10−15 | 30 | 406 |
ROR2 | 476 | 738 | 264 | 1.59 × 10−20 | 31 | 405 |
Candidate | Function | References |
---|---|---|
ANK3 | Ankyrin-3 (ANK3) regulates dendrites morphology and N-methyl-D-aspartate (NMDA) receptor trafficking. ANK3 participates in the formation and maintenance of the axon initial segment (AIS) and the nodes of Ranvier. Some mutant variants of the ANK3 gene have been associated with neurological disorders such as schizophrenia and autism. | [29,30] |
BMPR1A/BMPR2 | Bone morphogenetic protein receptor type 1A (BMPR1A) and type 2 (BMPR2) are receptors for the bone morphogenetic proteins (BMPs). The BMP signaling pathway induces the formation of the dorso-ventral axis of the developing spinal cord and brain, neurogenesis, and later astrogliogenesis, and it participates in neurite outgrowth from immature neurons. Inhibition of BMP signaling during early development promotes neuroectoderm-from-ectoderm differentiation. | [31] |
CSF1R | Colony-stimulating factor 1 receptor (CSF1R) is the receptor for the colony-stimulating factor 1 (CSF1) cytokine, which controls the generation, differentiation, and function of macrophages. In the central nervous system (CNS), CSF1 is a major regulator of microglial development and maintenance. Meanwhile, CSF1R is expressed in neural progenitor cells (NPCs). Mice lacking CSF1R exhibit global defects in brain development, including atrophy of the olfactory bulb, expansion of the lateral ventricle, thinning of the neocortex, and functional abnormalities of the sensory nervous system. | [32] |
EPHA2-5/EPHB2 | The erythropoietin-producing hepatocellular (EPH) family of tyrosine kinases receptors (RTKs) includes several members. EPH-B2 is expressed in hippocampal astrocytes, and it regulates neurogenesis and promotes neuronal differentiation of neural stem cells (NSCs). These receptors regulate cell migration by promoting changes in cellular adhesion to the extracellular matrix. They are also involved in the remodeling of efferent axons to ensure the correct and precise innervations to their target cells, in dendritic spine morphology, in synaptogenesis, and in synapse stabilization. | [33] |
FGFR2 | Fibroblast growth factor receptor 2 (FGFR2) controls neuronal morphological maturation, neuronal migration, and spine density during cortical development by interacting with the neuronal growth regulator 1 (NEGR1) protein. | [34] |
HHMGB1 | High mobility group box 1 (HHGB1) is required for the differentiation and proliferation of NSCs and NPCs. It also promotes neurite outgrowth during early forebrain development. | [35] |
HSP90AA1 (HSP90α) | Heat shock protein 90 alpha family class A member 1 (HSP90AA1) is induced by stress and can be expressed in the brain, retina, and spinal cord. It is highly expressed between the G0 and G1 cell cycle phases during embryonic neurodevelopment which correlate with neuronal differentiation and polarization. It also promotes neurite growth. | [36,37] |
HSP90AB1 (HSP90β) | Heat shock protein 90 alpha family class B member 1 (HSP90AB1) is highly and constitutively expressed in the brain, the retina, and the spinal cord between the G0 and the G1 phases of the cell cycle during embryonic neurodevelopment. It stabilizes and controls the activity of hypoxia inducible factor-1 (HIF-1) to promote NPC proliferation. | [38] |
LYN | Lyn expression is relatively low in the brains of embryonic and neonatal mice. However, at the protein level, LYN has been suggested to participate in the formation and function of synapses between granule and Purkinje cells in the rat cerebellum, resulting in motor learning. | [39,40] |
NOTCH1-3 receptor | The NOTCH receptor signaling pathway keeps NSCs in a proliferative state by promoting their survival and self-renewal. This pathway also has a role in defining cell fate (neuronal or glial). Briefly, it induces the expression of HES1 and HES5, which repress the expression of proneural genes and therefore inhibit neural differentiation. | [41] |
NRDC | Nardilysin convertase (NRDC) is a regulator of axonal maturation and myelination of both the CNS and the peripherical nervous system (PNS). Axon diameter and myelin thickness correlate with NRDC expression levels. It also participates in the proteolysis of NGR1, which is a regulator of myelination. | [42] |
NTRK1 | Neurotrophic receptor tyrosine kinase type 1 (NTRK1), also known as TRKA, belongs to a family of nerve growth-factor receptors whose ligands include neurotrophins, like the nerve growth factor (NGF), which is involved in the regulation of the development of central and peripheral neurons. | [43] |
ROR1-2 | Receptor tyrosine kinase-like orphan receptors (RORs) 1 and 2 are expressed exclusively in the developing nervous system, including in the mouse neocortex. It also regulates neurite extension and synapse formation in hippocampal neurons. The ROR1-WNT5a and ROR2-WNT5a signaling pathways regulate the maintenance of the proliferative and neurogenic states of NPCs. | [44] |
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Meza-Sosa, K.F.; Valle-Garcia, D.; González-Conchillos, H.; Blanco-Ayala, T.; Salazar, A.; Flores, I.; Gómez-Manzo, S.; González Esquivel, D.F.; Pérez de la Cruz, G.; Pineda, B.; et al. Molecular Mimicry by Toxoplasma gondii B-Cell Epitopes of Neurodevelopmental Proteins: An Immunoinformatic Approach. Biomolecules 2024, 14, 933. https://doi.org/10.3390/biom14080933
Meza-Sosa KF, Valle-Garcia D, González-Conchillos H, Blanco-Ayala T, Salazar A, Flores I, Gómez-Manzo S, González Esquivel DF, Pérez de la Cruz G, Pineda B, et al. Molecular Mimicry by Toxoplasma gondii B-Cell Epitopes of Neurodevelopmental Proteins: An Immunoinformatic Approach. Biomolecules. 2024; 14(8):933. https://doi.org/10.3390/biom14080933
Chicago/Turabian StyleMeza-Sosa, Karla F., David Valle-Garcia, Hugo González-Conchillos, Tonali Blanco-Ayala, Alelí Salazar, Itamar Flores, Saúl Gómez-Manzo, Dinora Fabiola González Esquivel, Gonzalo Pérez de la Cruz, Benjamín Pineda, and et al. 2024. "Molecular Mimicry by Toxoplasma gondii B-Cell Epitopes of Neurodevelopmental Proteins: An Immunoinformatic Approach" Biomolecules 14, no. 8: 933. https://doi.org/10.3390/biom14080933