Stockholm university

David DrewProfessor of Biochemistry

Research

Structure and Mechanism of Solute Carrier (SLC) Transporters

SLC transporters are the targets for many therapeutics and they often play a major role in drug pharmacokinetics. Understanding the mechanisms by which SLC 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 mechanistic understanding is very limited. The goal of my research is to investigate the alternating-access mechanism of solute transporters for sugars and ions, which are critical to cell homeostasis and their dysfunction is associated with human diseases, such as cancer and diabetes. To achieve this we combine crystal and cryo EM structures with biochemical and biophysical techniques. These goals are facilitated by the development of novel methods to aid functional and structural investigation of SLC transporters.

Popular descriptions of our work on transporters 

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

https://www.nature.com/articles/d41586-020-00148-8

https://www.nature.com/articles/d41586-023-03154-8

 

Current group members

Magnus Claesson, Lab Manager

Dohwan Ahn, Postdoc

Claudia Alleva, Postdoc

Marta Bonaccorsi, Postdoc

Ashutosh Gulati, Postdoc

Ved Mehta, Postdoc

Tom Reichenbach, Postdoc

Albert Suades, Postdoc

Sukkyeong Jung, PhD Student

Surabhi Kokane, PhD Student

 

Selected Publications

Gulati A, Kokane S, Boerema A.P, Alleva C, Meier P.F, Matsuoka R, Drew D(2024). Structure and mechanism of the K+/H+ exchanger KefC. Nature Communications 15: 4751.

Drew D, Boudker O. (2024). Ion and Lipid Orchestration of Secondary Active Transport. Nature 626: 963-974

Yeo H, Mehta V, Gulati A, Drew D(2023). Structure and mechanism of a voltage-gated Na+/H+ exchangerNature 623: 193-201.

Suades A, Qureshi A, McComas S. Coincon M, Rudling A, Chatzikyriakidou Y, Landreh M, Carlsson J, Drew D(2023). Establishing mammalian GLUT kinetics and lipid preferences in a reconstituted-liposome systemNature Communications 14: 4070.

Winkelmann I,  Uzdavinys P, Kenney I.M, Brock J, Meier P.F, Wagner L.M, Gabriel F, Jung S, Matsuoka M, von Ballmoos C, Beckstein O, Drew D(2022). Crystal structure of the Na+/Hantiporter NhaA at active pH reveals the mechanistic basis for pH sensingNaturCommunications. 13: 6383.

Asami J, Kimura K, Fujita Y, Ishida H, Zhang Z, Nomura Y, Liu K, Uemura T, Sato Y, Ono M, Yamamoto M, Noda T, Shigematsu H, Drew D, Iwata S, Shimizu T, Nomura N, Ohto U (2022) Structure of the bile acid transporter and HBV receptor NTCPNature. 606: 1021–1026

Matsuoka R, Fudim R, … , Beckstein O, Drew D (2022)Structure, mechanism and lipid-mediated re-modelling of the mammalian Na+/H+ exchanger NHA2. Nature Struct Mol Biol29:108-20.

Winklemann I, Matsuoka R, Meier P, Shutin D, Zhang C, Orellana L, Sexton R, Landreh M, Robinson C.V, Beckstein O, Drew DStructure and Elevator Mechanism of the Mammalian Sodium/Proton Exchanger NHE9 (2020). EMBO Journal39:4541-4559.

Qureshi A, Suades A, … , Delemotte L, Drew D (2020)The molecular basis for sugar import in malaria parasitesNature 578:321-25. 

Nji E, Gulati A, Qureshi A. Coincon, M, Drew D (2019)Structural basis for the delivery of activated sialic acid into Golgi lumenNature Struct Mol Biol. 26:415-23. 

Gupta G, Donlan J.A, Hopper J, Uzdavinys P, Landreh M, Struwe W, Drew D, Baldwin A, Stansfield P, Robinson C.V (2017). The role of interfacial lipids in stabilising membrane protein oligomersNature541:421-424

Coincon M, Uzdavinys P, … , Beckstein O, Drew D (2016) Crystal structures reveal the molecular basis of ion-translocation in sodium/proton antiportersNature Struct Mol Biol. 23:248-55. 

Nomura N, Verdon G, Kang HJ, … , Drew D (2015)Structure and mechanism of the mammalian fructose transporter GLUT5Nature526:397-401.

Lee C, Kang HJ, … , Cameron A, Drew D (2013). A two-domain elevator mechanism for sodium/proton antiport. Nature501:573-7. 

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

 

Commentaries and Reviews

Drew D (2022)Structures show how salt gets a sweet ride. Nature 601, 194-196.

Drew D, North R, Nagarathinam K, Tanabe K (2021)Structures and general transport mechanisms by the major facilitator superfamilyChemical Reviews121:5289–335.

Drew D, Boudker O (2016). Shared Molecular Mechanisms of Membrane Transporters Annual Reviews in Biochemistry. 85:543-72.

 

Funding Sources

Göran Gustaffson Foundation
Swedish Research Council
The Knut and Alice Wallenberg Foundation
The Cancer Foundation