Posters
Presenting Author Academic/Professional Position
Medical Student
Academic Level (Author 1)
Medical Student
Academic Level (Author 2)
Faculty
Presentation Type
Poster
Discipline Track
Biomedical Science
Abstract Type
Research/Clinical
Abstract
Neurological disorders are diseases of the central or peripheral nervous system caused by dysfunction in the brain, spinal cord, or other nervous tissue. Due to the dynamic nature of neurons and their highly specialized structure and function, piecing together the underlying cause of these disorders is difficult. The dysfunction of neuronal synapses, which are specialized structures that allow the transfer of information between neurons--either electrically or chemically--are believed to contribute to brain diseases. More specifically, excitatory glutamatergic synapses have been implicated in causing neuronal cell death under conditions of excess glutamate. Thus, glutamate receptors like the NMDA receptors and their regulations have become the subject of extensive research because of their potential as future therapies. The MAGUK (Membrane-Associated Guanylate Kinase) protein family, which consists of PSD93, PSD95, SAP97, and SAP102, functions to regulate the localization and function of these key receptors. SAP102 is a highly mobile MAGUK predominate in early synaptogenesis and its N-terminus contains a concentrated cluster of cysteine and histidine residues for metal binding. This study investigates the effect of zinc cations on modulating N-terminal domain of SAP102 (SAP102NT) to further elucidate the role that zinc cations may play in the central nervous system through a direct interaction with SAP102. The SAP102NT proteins were overexpressed and purified by affinity chromatography. The experiments of Zn2+ binding with SAP102NT were performed by fluorescence and NMR titrations and further confirmed by mutagenesis assays. The results show that zinc binds tightly to the N-terminus of SAP-102 with a binding affinity (Kd) in the micromolar range, suggesting that zinc is likely to serve a functional modulator of SAP-102 at synaptic sites implicated in its function of regulating glutamate receptors.
Recommended Citation
Karkoutly, Mohammad Y. and Zhang, Yonghong, "Structural Studies of Zinc Cations Modulating the N-terminal of Synapse-Associated Protein 102 (SAP102)" (2025). Research Symposium. 111.
https://scholarworks.utrgv.edu/somrs/2025/posters/111
Included in
Structural Studies of Zinc Cations Modulating the N-terminal of Synapse-Associated Protein 102 (SAP102)
Neurological disorders are diseases of the central or peripheral nervous system caused by dysfunction in the brain, spinal cord, or other nervous tissue. Due to the dynamic nature of neurons and their highly specialized structure and function, piecing together the underlying cause of these disorders is difficult. The dysfunction of neuronal synapses, which are specialized structures that allow the transfer of information between neurons--either electrically or chemically--are believed to contribute to brain diseases. More specifically, excitatory glutamatergic synapses have been implicated in causing neuronal cell death under conditions of excess glutamate. Thus, glutamate receptors like the NMDA receptors and their regulations have become the subject of extensive research because of their potential as future therapies. The MAGUK (Membrane-Associated Guanylate Kinase) protein family, which consists of PSD93, PSD95, SAP97, and SAP102, functions to regulate the localization and function of these key receptors. SAP102 is a highly mobile MAGUK predominate in early synaptogenesis and its N-terminus contains a concentrated cluster of cysteine and histidine residues for metal binding. This study investigates the effect of zinc cations on modulating N-terminal domain of SAP102 (SAP102NT) to further elucidate the role that zinc cations may play in the central nervous system through a direct interaction with SAP102. The SAP102NT proteins were overexpressed and purified by affinity chromatography. The experiments of Zn2+ binding with SAP102NT were performed by fluorescence and NMR titrations and further confirmed by mutagenesis assays. The results show that zinc binds tightly to the N-terminus of SAP-102 with a binding affinity (Kd) in the micromolar range, suggesting that zinc is likely to serve a functional modulator of SAP-102 at synaptic sites implicated in its function of regulating glutamate receptors.
