Crystal structure of a bacterial homologue of glucose transporters GLUT1-4

Sun, L. et al Nature 490, 361-366 (2012)

Speaker: Hsin-Pei Hsieh (謝欣倍)                                Time: 13:10~14:00, Mar. 20, 2013

Commentator: Dr. Wen-Yih Jeng (鄭文義 老師)        Place: Room 601

Abstract

Glucose is widely used as an energy source in cells. Uptake of glucose into cells is mediated by glucose transporter (GULT) and sodium-glucose co-transporter (SGLT) transporter families. The GLUT protein family is characterized as the major glucose transporter family in the membrane. At least 14 GLUT proteins have been identified in human¹. The roles of GLUT1-4 proteins in physiological and pathophysiological processes have been well studied. Mutations of GLUT1-4 proteins result in several diseases such as De Vivo disease and type 2 diabetes mellitus. Despite the vital role of GULT1-4, the structure and transport mechanism is still unclear due to the difficulties of obtaining GULT protein crystals. Therefore, the authors crystallize XylE protein, which shares highly sequence identities and similarities with GULT1-4. The structures of XylE bound to three different ligands: D-xylose, D-glucose, and 6-BrGlc are reported at resolutions 2.8, 2.9 and 2.6Å, respectively. Based on the XylE ligand-bound complex model, the authors built the XylE-based structural model of GULT1, and reveal significant findings. First, the GULT1 model contains four intracellular α-helices that were absent from previous LacY-based models². Second, transmembrane (TM) domain 7 is important in substrate coordination by contributing polar and aromatic residues. Third, in contrasts to previous prediction, the disease-related mutations participate in substrate transport not involve in substrate binding. Therefore, this XylE-based structural model of GULT1 leads to better understanding of glucose transport related diseases and provides basis of drug development.

References

1.      Thorens, B. & Mueckler, M. Glucose transporters in the 21st Century. Am. J. Physiol. Endocrinol. Metab. 298, E141–145 (2010).

2.      Abramson, J. et al. Structure and Mechanism of the Lactose Permease of Escherichia coli. Science 301, 610-615 (2003)