3QS6

Crystal structure of LeuT mutant F259V,I359Q bound to sodium and L-tryptophan

3QS6 の概要

• エントリーDOI: 10.2210/pdb3qs6/pdb
• 関連するPDBエントリー: 2A65 3F3A 3QS4 3QS6
• 分子名称: Na(+):neurotransmitter symporter (Snf family), TRYPTOPHAN, SODIUM ION, ... (5 entities in total)
• 機能のキーワード: nss, neurotransmitter transporter, leut-fold, sodium-coupled secondary transporter, sodium and amino acid binding, membrane, transport protein
• 由来する生物種: Aquifex aeolicus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 59171.68

構造登録者

Piscitelli, C.L.,Gouaux, E. (登録日: 2011-02-19, 公開日: 2011-10-12, 最終更新日: 2023-09-13)

主引用文献

Piscitelli, C.L.,Gouaux, E.
Insights into transport mechanism from LeuT engineered to transport tryptophan.
Embo J., 31:228-235, 2012

PubMed Abstract: LeuT is a bacterial homologue of the neurotransmitter:sodium symporter (NSS) family and, being the only NSS member to have been structurally characterized by X-ray crystallography, is a model protein for studying transporter structure and mechanism. Transport activity in LeuT was hypothesized to require structural transitions between open-to-out and occluded conformations dependent upon protein:ligand binding complementarity. Here, using crystallographic and functional analysis, we show that binding site modification produces changes in both structure and activity that are consistent with complementarity-dependent structural transitions to the occluded state. The mutation I359Q converts the activity of tryptophan from inhibitor to transportable substrate. This mutation changes the local environment of the binding site, inducing the bound tryptophan to adopt a different conformer than in the wild-type complex. Instead of trapping the transporter open, tryptophan binding now allows the formation of an occluded state. Thus, transport activity is correlated to the ability of the ligand to promote the structural transition to the occluded state, a step in the transport cycle that is dependent on protein:ligand complementarity in the central binding site.

PubMed: 21952050
DOI: 10.1038/emboj.2011.353

実験手法

X-RAY DIFFRACTION (2.801 Å)