6WW5

Structure of VcINDY-Na-Fab84 in nanodisc

Summary for 6WW5

• Entry DOI: 10.2210/pdb6ww5/pdb
• EMDB information: 21928
• Descriptor: DASS family sodium-coupled anion symporter, Fab84 Heavy Chain, Fab84 Light Chain, ... (6 entities in total)
• Functional Keywords: transporter, membrane protein
• Biological source: Vibrio cholerae; More
• Total number of polymer chains: 6
• Total formula weight: 205401.54

Authors

Sauer, D.B.,Marden, J.,Song, J.M.,Koide, A.,Koide, S.,Wang, D.N. (deposition date: 2020-05-07, release date: 2020-09-16, Last modification date: 2024-10-23)

Primary citation

Sauer, D.B.,Trebesch, N.,Marden, J.J.,Cocco, N.,Song, J.,Koide, A.,Koide, S.,Tajkhorshid, E.,Wang, D.N.
Structural basis for the reaction cycle of DASS dicarboxylate transporters.
Elife, 9:-, 2020

PubMed Abstract: Citrate, α-ketoglutarate and succinate are TCA cycle intermediates that also play essential roles in metabolic signaling and cellular regulation. These di- and tricarboxylates are imported into the cell by the divalent anion sodium symporter (DASS) family of plasma membrane transporters, which contains both cotransporters and exchangers. While DASS proteins transport substrates via an elevator mechanism, to date structures are only available for a single DASS cotransporter protein in a substrate-bound, inward-facing state. We report multiple cryo-EM and X-ray structures in four different states, including three hitherto unseen states, along with molecular dynamics simulations, of both a cotransporter and an exchanger. Comparison of these outward- and inward-facing structures reveal how the transport domain translates and rotates within the framework of the scaffold domain through the transport cycle. Additionally, we propose that DASS transporters ensure substrate coupling by a charge-compensation mechanism, and by structural changes upon substrate release.

PubMed: 32869741
DOI: 10.7554/eLife.61350

Experimental method

ELECTRON MICROSCOPY (3.15 Å)