5JAE

LeuT in the outward-oriented, Na+-free return state, P21 form at pH 6.5

5JAE の概要

• エントリーDOI: 10.2210/pdb5jae/pdb
• 分子名称: Transporter, octyl beta-D-glucopyranoside (3 entities in total)
• 機能のキーワード: membrane protein, neurotransmitter:sodium symporter family, amino acid transporter
• 由来する生物種: Aquifex aeolicus (strain VF5)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 119370.93

構造登録者

Malinauskaite, L.,Sahin, C.,Said, S.,Grouleff, J.,Shahsavar, A.,Bjerregaard, H.,Noer, P.,Severinsen, K.,Boesen, T.,Schiott, B.,Sinning, S.,Nissen, P. (登録日: 2016-04-12, 公開日: 2016-06-01, 最終更新日: 2024-01-10)

主引用文献

Malinauskaite, L.,Said, S.,Sahin, C.,Grouleff, J.,Shahsavar, A.,Bjerregaard, H.,Noer, P.,Severinsen, K.,Boesen, T.,Schitt, B.,Sinning, S.,Nissen, P.
A conserved leucine occupies the empty substrate site of LeuT in the Na(+)-free return state.
Nat Commun, 7:11673-11673, 2016

PubMed Abstract: Bacterial members of the neurotransmitter:sodium symporter (NSS) family perform Na(+)-dependent amino-acid uptake and extrude H(+) in return. Previous NSS structures represent intermediates of Na(+)/substrate binding or intracellular release, but not the inward-to-outward return transition. Here we report crystal structures of Aquifex aeolicus LeuT in an outward-oriented, Na(+)- and substrate-free state likely to be H(+)-occluded. We find a remarkable rotation of the conserved Leu25 into the empty substrate-binding pocket and rearrangements of the empty Na(+) sites. Mutational studies of the equivalent Leu99 in the human serotonin transporter show a critical role of this residue on the transport rate. Molecular dynamics simulations show that extracellular Na(+) is blocked unless Leu25 is rotated out of the substrate-binding pocket. We propose that Leu25 facilitates the inward-to-outward transition by compensating a Na(+)- and substrate-free state and acts as the gatekeeper for Na(+) binding that prevents leak in inward-outward return transitions.

PubMed: 27221344
DOI: 10.1038/ncomms11673

実験手法

X-RAY DIFFRACTION (2.5 Å)