Structure and Mechanism of the Divalent Anion/Na+ Symporter
Department of Biochemistry and Molecular Biology, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064, USA
Int. J. Mol. Sci. 2019, 20(2), 440; https://doi.org/10.3390/ijms20020440
Received: 21 December 2018
/
Revised: 14 January 2019
/
Accepted: 18 January 2019
/
Published: 21 January 2019
(This article belongs to the Section Molecular Biology)
Integral membrane proteins of the divalent anion/Na+ symporter (DASS) family are conserved from bacteria to humans. DASS proteins typically mediate the coupled uptake of Na+ ions and dicarboxylate, tricarboxylate, or sulfate. Since the substrates for DASS include key intermediates and regulators of energy metabolism, alterations of DASS function profoundly affect fat storage, energy expenditure and life span. Furthermore, loss-of-function mutations in a human DASS have been associated with neonatal epileptic encephalopathy. More recently, human DASS has also been implicated in the development of liver cancers. Therefore, human DASS proteins are potentially promising pharmacological targets for battling obesity, diabetes, kidney stone, fatty liver, as well as other metabolic and neurological disorders. Despite its clinical relevance, the mechanism by which DASS proteins recognize and transport anionic substrates remains unclear. Recently, the crystal structures of a bacterial DASS and its humanized variant have been published. This article reviews the mechanistic implications of these structures and suggests future work to better understand how the function of DASS can be modulated for potential therapeutic benefit.
View Full-Text
Keywords:
membrane protein; anion transporter; sodium symporter; dicarboxylate transporter; substrate recognition; sodium coordination
▼
Show Figures
Figure 1
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
MDPI and ACS Style
Lu, M. Structure and Mechanism of the Divalent Anion/Na+ Symporter. Int. J. Mol. Sci. 2019, 20, 440. https://doi.org/10.3390/ijms20020440
AMA Style
Lu M. Structure and Mechanism of the Divalent Anion/Na+ Symporter. International Journal of Molecular Sciences. 2019; 20(2):440. https://doi.org/10.3390/ijms20020440
Chicago/Turabian StyleLu, Min. 2019. "Structure and Mechanism of the Divalent Anion/Na+ Symporter" International Journal of Molecular Sciences 20, no. 2: 440. https://doi.org/10.3390/ijms20020440
Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.
