Woo Ju Rang, Kim Soon-Jong, Kim Keon Young, Jang Hyonchol, Shoelson Steven E, Park SangYoun
Division of Development and Optimization, New Drug Development Center, KBIO Health, Chungbuk 28160, Republic of Korea.
Department of Chemistry, Mokpo National University, Chonnam 58554, Republic of Korea.
Int J Biol Macromol. 2017 Oct;103:965-971. doi: 10.1016/j.ijbiomac.2017.05.119. Epub 2017 May 22.
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.
TBC1D4（也称为AS160）是一种在胰岛素信号传导中发挥作用的Rab·GTPase激活蛋白（RabGAP）。TBC1D4对于葡萄糖转运蛋白4（GLUT4）从无活性的细胞内囊泡结合位点转运到质膜至关重要，在质膜上它促进葡萄糖进入细胞。TBC1D4蛋白在结构上可细分为两个N端磷酸酪氨酸结合（PTB）结构域、一个C端催化RabGAP结构域以及两者之间包含潜在Akt磷酸化位点的无序区段。结构预测进一步表明，RabGAP结构域C端的一个区域采用卷曲螺旋基序。我们发现C端区域（CTR）主要是α螺旋结构，并介导TBC1D4 RabGAP二聚化。RabGAP催化活性和热稳定性似乎与CTR介导的二聚化无关。
