Research

Structure and Mechanism of Solute Carrier (SLC) Transporters

Secondary transporters are the targets for many therapeutics and they often play a major role in drug pharmacokinetics. Understanding the mechanisms by which secondary transporters shuttle and move ions, drugs, and natural compounds across membranes is of fundamental importance. Because of the technical difficulties in working with membrane proteins our structural understanding is very limited. The goal of my research is to investigate the alternating access-mechanism of solute transporters which are critical to cell homeostasis and their dysfunction is associated with human diseases, such as cancer and cardiovascular heart disease. To achieve this we combine crystal structures with biochemical and biophysical techniques. These goals are facilitated by the development of novel methods in membrane protein overexpression, purification and crystallization.

Popular descriptions of our work on transporters 

https://www.youtube.com/watch?v=fwW86e3tFv4

https://www.su.se/forskning/profilområden/biologiska-membraner/forskning-som-lär-oss-mer-om-cellens-dörrar-1.347363

Group members

Magnus Claesson, Lab Manager

Dohwan Ahn, Postdoc

Ashutosh Gulati, Postdoc

Rei Matsuoka, Postdoc

Emmanuel Nji, Postdoc

Jan Skerle, Postdoc

Albert Suades, Postdoc

Hyunku Yeo, Postdoc

Yurie Chatzikyriakidou, PhD Student

Sarah McComas, PhD Student

Pascal Meier, PhD Student

Abdul Aziz Qureshi, PhD Student

Iven Winkelmann, PhD Student

Selected Publications

Nji E, Chatzikyriakidou Y, Landreh M, Drew D. An engineered thermal shift screen reveals specific lipid preferences of eukaryotic and prokaryotic membrane proteins. Nature Communications. 9:4253 (2018)

Uzdavinys P, Coincon C, Nji E, Ndi M, Winkelman I, von Ballmoos C, Drew D. Dissecting the proton transport pathway in electrogenic Na+/H+ antiporters. Proc Natl Acad Sci U S A. (2017) Feb 14;114(7):E1101-E1110.

Gupta G, Donlan J.A, Hopper J, Uzdavinys P, Landreh M, Struwe W, Drew D, Stansfeld P, Robinson C.V. The role of interfacial lipids in stabilising membrane protein oligomers. Nature (2017). Jan 19;541(7637):421-424.

Landreh M, Marklund E, Uzdavinys P, Degiacomi M, Coincon M, Liko I, Benesch J, Drew D, Robinson C.V Integrating mass spectrometry and MD simulations reveals the role of lipids in Na+/H+ antiporters. Nature Communications (2017) Jan 10;8:13993.

Drew D, Boudker O. Shared Molecular Mechanisms of Membrane Transporters. Annual Reviews in Biochemistry. (2016). Mar 21 85(1).

Coincon M, Uzdavinys P, Nji E, Dotson D.L, Winkelmann I, Abdul-Hussein S, Cameron A.D, Beckstein O, Drew D. Crystal structures reveal the molecular basis of ion-translocation in sodium/proton antiporters. Nature Structure & Molecular Biology. (2016) Mar:23(3):248-55.

Nomura N, Verdon G, Kang HJ, Shimamura T, Nomura Y, Sonoda Y, Hussien S, Qureshi A.A, Coincon M, Sato Y, Abe H, Nakada-Nakura Y, Hino T, Arakawa T, Kusano-Arai O, Iwanari H, Unno H, Murata T, Kobayashi T, Hamakubo T, Kasahara M, Iwata S, Drew D. Structure and mechanism of the mammalian fructose transporter GLUT5. Nature (2015) 526(7573):397-401.             

Lee C, Kang HJ, von Ballmoos C, Newstead S, Uzdavinys P, Dotson D, Iwata S, Beckstein O, Cameron A.D, Drew D. A two-domain elevator mechanism for sodium/proton antiport. Nature (2013) Sept 26:501(7468):573-7.

Hu NJ, Iwata S, Cameron A.D, Drew D. Crystal structure of a bacterial homologue of the bile acid sodium symporter ASBT. Nature (2011). Oct 3:478:408-11.

Funding Sources