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Int J Biol Macromol. 2017 Oct;103:965-971. doi: 10.1016/j.ijbiomac.2017.05.119. Epub 2017 May 22.

The carboxy-terminal region of the TBC1D4 (AS160) RabGAP mediates protein homodimerization.

Author information

1
Division of Development and Optimization, New Drug Development Center, KBIO Health, Chungbuk 28160, Republic of Korea.
2
Department of Chemistry, Mokpo National University, Chonnam 58554, Republic of Korea.
3
School of Systems Biomedical Science, Soongsil University, Seoul 06978, Republic of Korea.
4
Division of Cancer Biology, Research Institute, National Cancer Center, Goyang, Gyeonggi 10408, Republic of Korea.
5
Joslin Diabetes Center & Department of Medicine, Harvard Medical School, Boston, MA 02215, USA.
6
School of Systems Biomedical Science, Soongsil University, Seoul 06978, Republic of Korea. Electronic address: psy@ssu.ac.kr.

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.

KEYWORDS:

AS160; Coiled-coil; Dimerization; RabGAP; TBC1D1; TBC1D4

PMID:
28545963
PMCID:
PMC5548637
DOI:
10.1016/j.ijbiomac.2017.05.119
[Indexed for MEDLINE]
Free PMC Article

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