Title
The carboxy-terminal region of the TBC1D4 (AS160) RabGAP mediates protein homodimerization
Author
Ju Rang Woo, Soon-Jong Kim, Keon Young Kim, Hyonchol Jang, Steven E. Shoelson, SangYoun Park
Year
2017
Journal
International Journal of Biological Macromolecules
Abstract
TBC1D4 (also known as AS160) is a Rab·GTPase-activating protein (RabGAP) which functions in insulin signaling. TBC1D4 is critical for translocation of glucose transporter 4 (GLUT4), from an inactive, intracellular, vesicle-bound site to the plasma membrane, where it promotes glucose entry into cells. The TBC1D4 protein is structurally subdivided into two N-terminal phosphotyrosine-binding (PTB) domains, a C-terminal catalytic RabGAP domain, and a disordered segment in between containing potential Akt phosphorylation sites. Structural predictions further suggest that a region C-terminal to the RabGAP domain adopts a coiled-coil motif. We show that C-terminal region (CTR) region is largely α-helical and mediates TBC1D4 RabGAP dimerization. RabGAP catalytic activity and thermal stability appear to be independent of CTR-mediated dimerization.
Instrument
J-810
Keywords
Circular dichroism, Secondary structure, Thermal stability, Thermodynamics, Protein folding, Biochemistry