PDBsum entry 4us4

Transport protein

PDB id: 4us4

Contents

Protein chain

433 a.a.

Ligands

TRP

78M ×2

78N

Metals

_NA ×2

Waters ×22

PDB id:

4us4

Name:

Transport protein

Title:

Crystal structure of the bacterial nss member mhst in an occluded inward-facing state (lipidic cubic phase form)

Structure:

Transporter. Chain: a. Synonym: multi-hydrophobic amino acid transporter. Engineered: yes

Source:

Bacillus halodurans. Organism_taxid: 272558. Strain: c-125. Atcc: baa-125. Expressed in: lactococcus lactis subsp. Cremoris nz9000. Expression_system_taxid: 746361.

Resolution:

2.60Å R-factor: 0.205 R-free: 0.255

Authors:

L.Malinauskaite,M.Quick,L.Reinhard,J.A.Lyons,H.Yano,J.A.Javitch, P.Nissen

Key ref:

L.Malinauskaite et al. (2014). A mechanism for intracellular release of Na+ by neurotransmitter/sodium symporters. Nat Struct Biol, 21, 1006-1012. PubMed id: 25282149 DOI: 10.1038/nsmb.2894

Date:

02-Jul-14 Release date: 24-Sep-14

Protein chain

Q9KDT3  (Q9KDT3_BACHD) -  Sodium-dependent transporter from Halalkalibacterium halodurans (strain ATCC BAA-125 / DSM 18197 / FERM 7344 / JCM 9153 / C-125)

Seq: 453 a.a.

Struc: 433 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1038/nsmb.2894

Nat Struct Biol 21:1006-1012 (2014)

PubMed id: 25282149

A mechanism for intracellular release of Na+ by neurotransmitter/sodium symporters.

L.Malinauskaite, M.Quick, L.Reinhard, J.A.Lyons, H.Yano, J.A.Javitch, P.Nissen.

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.