4US3

Crystal Structure of the bacterial NSS member MhsT in an Occluded Inward-Facing State

Summary for 4US3

• Entry DOI: 10.2210/pdb4us3/pdb
• Related: 4US4
• Descriptor: TRANSPORTER, TRYPTOPHAN, SODIUM ION, ... (6 entities in total)
• Functional Keywords: transport protein, neurotransmitter, neurotransmitter sodium symporter family, leut fold, amino acid transporter, secondary transporter, membrane protein
• Biological source: BACILLUS HALODURANS
• Total number of polymer chains: 1
• Total formula weight: 52900.32

Authors

Malinauskaite, L.,Quick, M.,Reinhard, L.,Lyons, J.A.,Yano, H.,Javitch, J.A.,Nissen, P. (deposition date: 2014-07-02, release date: 2014-09-24, Last modification date: 2024-01-10)

Primary citation

Malinauskaite, L.,Quick, M.,Reinhard, L.,Lyons, J.A.,Yano, H.,Javitch, J.A.,Nissen, P.
A Mechanism for Intracellular Release of Na+ by Neurotransmitter/Sodium Symporters
Nat.Struct.Mol.Biol., 21:1006-, 2014

PubMed Abstract: Neurotransmitter/sodium symporters (NSSs) terminate synaptic signal transmission by Na+-dependent reuptake of released neurotransmitters. Key conformational states have been reported for the bacterial homolog LeuT and an inhibitor-bound Drosophila dopamine transporter. However, a coherent mechanism of Na+-driven transport has not been described. Here, we present two crystal structures of MhsT, an NSS member from Bacillus halodurans, in occluded inward-facing states with bound Na+ ions and L-tryptophan, providing insight into the cytoplasmic release of Na+. The switch from outward- to inward-oriented states is centered on the partial unwinding of transmembrane helix 5, facilitated by a conserved GlyX9Pro motif that opens an intracellular pathway for water to access the Na2 site. We propose a mechanism, based on our structural and functional findings, in which solvation through the TM5 pathway facilitates Na+ release from Na2 and the transition to an inward-open state.

PubMed: 25282149
DOI: 10.1038/NSMB.2894

Experimental method

X-RAY DIFFRACTION (2.098 Å)