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
Selected Publications
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+/H+ antiporter NhaA at active pH reveals the mechanistic basis for pH sensing. Nature Communications. 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 NTCP. Nature. 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 Biol. 29:108-20.
Winklemann I, Matsuoka R, Meier P, Shutin D, Zhang C, Orellana L, Sexton R, Landreh M, Robinson C.V, Beckstein O, Drew D. Structure 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 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. Nature 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 oligomers. Nature. 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. Nature Struct Mol Biol. 23:248-55.
Nomura N, Verdon G, Kang HJ, … , Drew D (2015). Structure and mechanism of the mammalian fructose transporter GLUT5. Nature. 526:397-401.
Lee C, Kang HJ, … , Cameron A, Drew D (2013). A two-domain elevator mechanism for sodium/proton antiport. Nature. 501:573-7.
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 Reviews. 121:5289–335.
Drew D, Boudker O (2016). Shared Molecular Mechanisms of Membrane Transporters Annual Reviews in Biochemistry. 85:543-72.