David Drew

Stockholm University

Keywords
Key publications

Matsuoka R, Fudim R, …, Drew D. Structure, mechanism and lipid-mediated re-modelling of the mammalian Na+/H+ exchanger NHA2. Nature Structure & Mol. Biology (2022).

 

Qureshi A, Suades A, …, Drew D. The molecular basis for sugar import in malaria parasites. Nature. 578 (7794):321-325. (2020)

 

Nji E, Gulati A, …, Drew D. Structural basis for the delivery of activated sialic acid into Golgi lumen. Nature Structure & Mol. Biology (2019) Jun;26(6):415-423.

 

Coincon M, Uzdavinys P,…, Drew D. Crystal structures reveal the molecular basis of ion-translocation in sodium/proton antiporters. Nature Structure & Mol. Biology (2016) Mar;23(3):248-55.

 

Nomura N, Verdon G, …, Drew D. Structure and mechanism of the mammalian fructose transporter GLUT5. Nature (2015) 526(7573):397-401.

 

Lee C, Kang HJ, …, Drew D. A two-domain elevator mechanism for sodium/proton antiport.

Nature (2013) 501(7468):573-7.

 

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

 

David Drew

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 Drew lab aims to understand the biophysical and chemical principles governing transporter function.

Solute transporters have to scan the cells surface to absorb only specific molecules out of all of the tens of millions of molecules they encounter. The Drew lab determined the first X-ray structures of a glucose (GLUT) transporter with doors open to both the outside and the inside of the cell. Drew has proposed a glucose transport mechanism and this model has been further refined by structures of a related malarial parasite sugar transporter with doors closed to both sides. GLUT transporters are responsible for maintaining blood glucose homeostasis in humans, and this work provides a foundation for their selective pharmacological control to combat human diseases, such as cancer and diabetes. His lab has further investigated how salt (sodium) is absorbed and exchanged for protons across cell membranes to control the cell’s internal pH by determining the first cryo-EM structures of mammalian Na+/H+ exchangers. These proteins operate very differently to the sugar transporters, and this work has aided in the general acceptance of an “elevator” transport mechanism, as first described in glutamate transporters.

The Drew lab will continue to combine cryo EM structures with biophysical and biochemical assays to deepen the mechanistic models for sugar and ion transport, and to establish how the activity of these proteins are regulated by interaction with other proteins and lipids. These goals are facilitated by the development of novel methods to aid in the functional and structural investigation of SLC transporters.

Funding

Knut och Alice Wallenberg, VR, ERC, Cancerfonden, Göran Gustafsson Foundation

Keywords

Membrane Proteins, Transporters, Structure, Mechanism, Drug interactions, Biotechnology, Biophysics

PhD students

Pascal Meier, cryo EM and ion transporters

Sarah McComas, MD simulations and sugar transporters

Surabhi Kokane, cryo EM and ion transporters

Sukkyeong Jung, cryo EM and ion transporters

PostDocs

Ashutosh Gulati, X-ray, cryo EM and ion transporters

Hyunku Yeo, cryo EM and ion transporters

Dohwan Ahn, X-ray, NMR and sugar transporters

Claudia Alleva, MD simulations and sugar transporters

Marta Bonaccorsi, NMR and MD simulations of sugar transporters

Rachel North, cryo EM and sugar transporters

Tom Reichenbach, cryo EM and sugar transporters

Albert Suades, biochemical assays and sugar transporters

Ved Mehta, cryo EM and ion transporters

Lab Manager

Magnus Claesson, X-ray and sugar transporters

Last updated: 2023-10-24

Content Responsible: David Gotthold(david.gotthold@scilifelab.se)