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Full-Text Articles in Life Sciences
The Neuronal Calcium Sensor Ncs-1 Regulates The Phosphorylation State And Activity Of The Gα Chaperone And Gef Ric-8a, Daniel Muñoz-Reyes, Levi J. Mcclelland, Sandra Arroyo-Urea, Sonia Sánchez-Yepes, Juan Sabín, Sara Pérez-Suárez, Margarita Menendez, Alicia Mansilla, Javier García-Nafría, Stephen Sprang, Maria Jose Sanchez-Barrena
The Neuronal Calcium Sensor Ncs-1 Regulates The Phosphorylation State And Activity Of The Gα Chaperone And Gef Ric-8a, Daniel Muñoz-Reyes, Levi J. Mcclelland, Sandra Arroyo-Urea, Sonia Sánchez-Yepes, Juan Sabín, Sara Pérez-Suárez, Margarita Menendez, Alicia Mansilla, Javier García-Nafría, Stephen Sprang, Maria Jose Sanchez-Barrena
Biological Sciences Faculty Publications
The neuronal calcium sensor 1 (NCS-1), an EF-hand Ca binding protein, and Ric-8A coregulate synapse number and probability of neurotransmitter release. Recently, the structures of Ric-8A bound to Gα have revealed how Ric-8A phosphorylation promotes Gα recognition and activity as a chaperone and guanine nucleotide exchange factor. However, the molecular mechanism by which NCS-1 regulates Ric-8A activity and its interaction with Gα subunits is not well understood. Given the interest in the NCS-1/Ric-8A complex as a therapeutic target in nervous system disorders, it is necessary to shed light on this molecular mechanism of action at atomic level. We have reconstituted …
Ric-8a, A G Protein Chaperone With Nucleotide Exchange Activity Induces Long-Range Secondary Structure Changes In Gα, Ravi Kant, Baisen Zeng, Celestine J. Thomas, Brian Bothner, Stephen R. Sprang
Ric-8a, A G Protein Chaperone With Nucleotide Exchange Activity Induces Long-Range Secondary Structure Changes In Gα, Ravi Kant, Baisen Zeng, Celestine J. Thomas, Brian Bothner, Stephen R. Sprang
Biological Sciences Faculty Publications
Cytosolic Ric-8A has guanine nucleotide exchange factor (GEF) activity and is a chaperone for several classes of heterotrimeric G protein α subunits in vertebrates. Using Hydrogen-Deuterium Exchange-Mass Spectrometry (HDX-MS) we show that Ric-8A disrupts the secondary structure of the Gα Ras-like domain that girds the guanine nucleotide-binding site, and destabilizes the interface between the Gαi1 Ras and helical domains, allowing domain separation and nucleotide release. These changes are largely reversed upon binding GTP and dissociation of Ric-8A. HDX-MS identifies a potential Gα interaction site in Ric-8A. Alanine scanning reveals residues crucial for GEF activity within that sequence. HDX confirms that, …