6OL1

Structure of VcINDY in complex with Succinate

Summary for 6OL1

• Entry DOI: 10.2210/pdb6ol1/pdb
• Descriptor: Transporter, NadC family, SODIUM ION, SUCCINIC ACID (3 entities in total)
• Functional Keywords: complex, transporter, membrane protein, transport protein
• Biological source: Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961)
• Total number of polymer chains: 4
• Total formula weight: 193285.71

Authors

Sauer, D.B.,Marden, J.J.,Wang, D.N. (deposition date: 2019-04-15, release date: 2020-10-28, Last modification date: 2026-02-25)

Primary citation

Kinz-Thompson, C.D.,Lopez-Redondo, M.L.,Mulligan, C.,Sauer, D.B.,Marden, J.J.,Song, J.,Tajkhorshid, E.,Hunt, J.F.,Stokes, D.L.,Mindell, J.A.,Wang, D.N.,Gonzalez Jr., R.L.
Elevator mechanism dynamics in a sodium-coupled dicarboxylate transporter.
Proc.Natl.Acad.Sci.USA, 123:e2500723123-e2500723123, 2026

PubMed Abstract: VcINDY, the sodium-dependent dicarboxylate transporter from , is responsible for C-carboxylate uptake into cells. The molecular mechanism of how VcINDY physically moves substrates across the membrane, and does so in an energetically efficient manner, is unclear. Here, we use single-molecule fluorescence resonance energy transfer experiments to directly observe the individual mechanistic steps that VcINDY takes to translocate substrates across a lipid bilayer, and then test key predictions of transport cycle mechanistic models. Our data provide the first direct, dynamic evidence that VcINDY undergoes stochastic, elevator-type conformational motions that enable substrate translocation. The dynamics of these elevator motions are approximately an order of magnitude faster than the turnover rate for substrate transport, demonstrating that VcINDY undergoes multiple rounds of substrate translocation before a productive transport cycle is completed. Furthermore, the two protomers of the VcINDY homodimer undergo the substrate translocation motions in a noncooperative manner, and thus likely engage in independent transport reactions. The relative substrate independence of those motions supports the notion that the VcINDY transport cycle maintains strict cosubstrate coupling by a mechanism other than translocation inhibition. Thermodynamic modeling provides insight into how a cooperative binding mechanism is one such generalized approach to optimizing transport for many secondary active transporters.

PubMed: 41490488
DOI: 10.1073/pnas.2500723123

Experimental method

X-RAY DIFFRACTION (3.088 Å)