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David DrewProfessor in 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.svd.se/genombrott-kan-leda-till-ny-malariamedicin

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

 

Current group members

Magnus Claesson, Lab Manager

Rachel North, Researcher

Dohwan Ahn, Postdoc

Claudia Alleva, Postdoc

Marta Bonaccorsi, Postdoc

Ashutosh Gulati, Postdoc

Ved Mehta, Postdoc

Tom Reichenbach, Postdoc

Albert Suades, Postdoc

Hyunku Yeo, Postdoc

Sukkyeong Jung, PhD Student

Surabhi Kokane, PhD Student

Sarah McComas, PhD Student

Pascal Meier, PhD Student

 

Selected Publications

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 hepatitis B virus entry receptor NTCP.

Nature. May 17th. 

 

Matsuoka R, Fudim R, … , Beckstein O, Drew D (2022)

Structure, mechanism and lipid-mediated re-modelling of the mammalian Na+/H+

exchanger NHA2.

Nat Struct Mol Biol29:108-20.

 

Qureshi A, Suades A, … , Delemotte L, Drew D (2020)

The molecular basis for sugar import in malaria parasites   

Nature 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 lumen

Nat 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. 

The role of interfacial lipids in stabilising membrane protein oligomers. 

Nature (2017). 541:421-424

 

Coincon M, Uzdavinys P, … , Beckstein O, Drew D (2016)

Crystal structures reveal the molecular basis of ion-translocation in sodium/proton antiporters

Nat Struct Mol Biol. 23:248-55. 

 

Nomura N, Verdon G, Kang HJ, … , Drew D (2015)

Structure and mechanism of the mammalian fructose transporter GLUT5  

Nature526:397-401.

 

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 ASBT 

Nature. 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 superfamily

Chemical 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
European Research Council
Swedish Research Council
The Knut and Alice Wallenberg Foundation
The Cancer Foundation