The Carboxy-terminal Region of the TBC1D4 (AS160) RabGAP Mediates Protein Homodimerization

Overview

Journal Int J Biol Macromol

Publisher Elsevier

Date 2017 May 27

PMID 28545963

Citations 4

Authors

Ju Rang Woo

Soon-Jong Kim

Keon Young Kim

Hyonchol Jang

Steven E Shoelson

SangYoun Park

Affiliations

Soon will be listed here.

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.

Citing Articles

Osteoblasts induce glucose-derived ATP perturbations in chondrocytes through noncontact communication.

Wei J, Yang Y, Guo D, Xu S, Huang H, Zhang D Acta Biochim Biophys Sin (Shanghai). 2022; 54(5):625-636.

PMID: 35593470 PMC: 9828329. DOI: 10.3724/abbs.2022042.

Illumination of the Endogenous Insulin-Regulated TBC1D4 Interactome in Human Skeletal Muscle.

Larsen J, Larsen M, Birk J, Steenberg D, Hingst J, Hojlund K Diabetes. 2022; 71(5):906-920.

PMID: 35192682 PMC: 9074744. DOI: 10.2337/db21-0855.

Cooperative actions of Tbc1d1 and AS160/Tbc1d4 in GLUT4-trafficking activities.

Hatakeyama H, Morino T, Ishii T, Kanzaki M J Biol Chem. 2018; 294(4):1161-1172.

PMID: 30482843 PMC: 6349102. DOI: 10.1074/jbc.RA118.004614.

AKT and AMP-activated protein kinase regulate TBC1D1 through phosphorylation and its interaction with the cytosolic tail of insulin-regulated aminopeptidase IRAP.

Mafakheri S, Florke R, Kanngiesser S, Hartwig S, Espelage L, de Wendt C J Biol Chem. 2018; 293(46):17853-17862.

PMID: 30275018 PMC: 6240868. DOI: 10.1074/jbc.RA118.005040.

References

Zerial M, McBride H . Rab proteins as membrane organizers. Nat Rev Mol Cell Biol. 2001; 2(2):107-17. DOI: 10.1038/35052055. View

Scrima A, Thomas C, Deaconescu D, Wittinghofer A . The Rap-RapGAP complex: GTP hydrolysis without catalytic glutamine and arginine residues. EMBO J. 2008; 27(7):1145-53. PMC: 2265111. DOI: 10.1038/emboj.2008.30. View

Sano H, Eguez L, Teruel M, Fukuda M, Chuang T, Chavez J . Rab10, a target of the AS160 Rab GAP, is required for insulin-stimulated translocation of GLUT4 to the adipocyte plasma membrane. Cell Metab. 2007; 5(4):293-303. DOI: 10.1016/j.cmet.2007.03.001. View

Daumke O, Weyand M, Chakrabarti P, Vetter I, Wittinghofer A . The GTPase-activating protein Rap1GAP uses a catalytic asparagine. Nature. 2004; 429(6988):197-201. DOI: 10.1038/nature02505. View

Terasawa M, Uruno T, Mori S, Kukimoto-Niino M, Nishikimi A, Sanematsu F . Dimerization of DOCK2 is essential for DOCK2-mediated Rac activation and lymphocyte migration. PLoS One. 2012; 7(9):e46277. PMC: 3458822. DOI: 10.1371/journal.pone.0046277. View

Kane S, Sano H, Liu S, Asara J, Lane W, Garner C . A method to identify serine kinase substrates. Akt phosphorylates a novel adipocyte protein with a Rab GTPase-activating protein (GAP) domain. J Biol Chem. 2002; 277(25):22115-8. DOI: 10.1074/jbc.C200198200. View

Sreerama N, Venyaminov S, Woody R . Estimation of the number of alpha-helical and beta-strand segments in proteins using circular dichroism spectroscopy. Protein Sci. 1999; 8(2):370-80. PMC: 2144265. DOI: 10.1110/ps.8.2.370. View

Dai Y, Walker S, de Vet E, Cook S, Welch H, Lockyer P . Ca2+-dependent monomer and dimer formation switches CAPRI Protein between Ras GTPase-activating protein (GAP) and RapGAP activities. J Biol Chem. 2011; 286(22):19905-16. PMC: 3103366. DOI: 10.1074/jbc.M110.201301. View

Perez-Iratxeta C, Andrade-Navarro M . K2D2: estimation of protein secondary structure from circular dichroism spectra. BMC Struct Biol. 2008; 8:25. PMC: 2397409. DOI: 10.1186/1472-6807-8-25. View

10.

Park S, Kim K, Kim S, Yu Y . Affinity between TBC1D4 (AS160) phosphotyrosine-binding domain and insulin-regulated aminopeptidase cytoplasmic domain measured by isothermal titration calorimetry. BMB Rep. 2012; 45(6):360-4. DOI: 10.5483/bmbrep.2012.45.6.030. View

11.

Miinea C, Sano H, Kane S, Sano E, Fukuda M, Peranen J . AS160, the Akt substrate regulating GLUT4 translocation, has a functional Rab GTPase-activating protein domain. Biochem J. 2005; 391(Pt 1):87-93. PMC: 1237142. DOI: 10.1042/BJ20050887. View

12.

Tan S, Ng Y, Burchfield J, Ramm G, Lambright D, Stockli J . The Rab GTPase-activating protein TBC1D4/AS160 contains an atypical phosphotyrosine-binding domain that interacts with plasma membrane phospholipids to facilitate GLUT4 trafficking in adipocytes. Mol Cell Biol. 2012; 32(24):4946-59. PMC: 3510527. DOI: 10.1128/MCB.00761-12. View

13.

Andrade M, Chacon P, Merelo J, Moran F . Evaluation of secondary structure of proteins from UV circular dichroism spectra using an unsupervised learning neural network. Protein Eng. 1993; 6(4):383-90. DOI: 10.1093/protein/6.4.383. View

14.

Stenmark H . Rab GTPases as coordinators of vesicle traffic. Nat Rev Mol Cell Biol. 2009; 10(8):513-25. DOI: 10.1038/nrm2728. View

15.

Gill S, von Hippel P . Calculation of protein extinction coefficients from amino acid sequence data. Anal Biochem. 1989; 182(2):319-26. DOI: 10.1016/0003-2697(89)90602-7. View

16.

Sano H, Roach W, Peck G, Fukuda M, Lienhard G . Rab10 in insulin-stimulated GLUT4 translocation. Biochem J. 2007; 411(1):89-95. DOI: 10.1042/BJ20071318. View

17.

Kulkarni K, Yang J, Zhang Z, Barford D . Multiple factors confer specific Cdc42 and Rac protein activation by dedicator of cytokinesis (DOCK) nucleotide exchange factors. J Biol Chem. 2011; 286(28):25341-51. PMC: 3137105. DOI: 10.1074/jbc.M111.236455. View

18.

Watson R, Pessin J . Bridging the GAP between insulin signaling and GLUT4 translocation. Trends Biochem Sci. 2006; 31(4):215-22. DOI: 10.1016/j.tibs.2006.02.007. View

19.

Knott G . Mlab--a mathematical modeling tool. Comput Programs Biomed. 1979; 10(3):271-80. DOI: 10.1016/0010-468x(79)90075-8. View

20.

Park S, Jin W, Woo J, Shoelson S . Crystal structures of human TBC1D1 and TBC1D4 (AS160) RabGTPase-activating protein (RabGAP) domains reveal critical elements for GLUT4 translocation. J Biol Chem. 2011; 286(20):18130-8. PMC: 3093885. DOI: 10.1074/jbc.M110.217323. View