3TT1

Crystal Structure of LeuT in the outward-open conformation in complex with Fab

3TT1 の概要

• エントリーDOI: 10.2210/pdb3tt1/pdb
• 関連するPDBエントリー: 2A65 3TT3 3TU0
• 分子名称: Leucine transporter LeuT, mouse monoclonal 1gG2a Fab fragment, heavy chain, mouse monoclonal 1gG2a Fab fragment, kappa light chain, ... (6 entities in total)
• 機能のキーワード: leut fold, transporter, plasma membrane, transport protein
• 由来する生物種: Aquifex aeolicus; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 212613.83

構造登録者

Krishnamurthy, H.,Gouaux, E. (登録日: 2011-09-13, 公開日: 2012-01-04, 最終更新日: 2024-11-06)

主引用文献

Krishnamurthy, H.,Gouaux, E.
X-ray structures of LeuT in substrate-free outward-open and apo inward-open states.
Nature, 481:469-474, 2012

PubMed Abstract: Neurotransmitter sodium symporters are integral membrane proteins that remove chemical transmitters from the synapse and terminate neurotransmission mediated by serotonin, dopamine, noradrenaline, glycine and GABA (γ-aminobutyric acid). Crystal structures of the bacterial homologue, LeuT, in substrate-bound outward-occluded and competitive inhibitor-bound outward-facing states have advanced our mechanistic understanding of neurotransmitter sodium symporters but have left fundamental questions unanswered. Here we report crystal structures of LeuT mutants in complexes with conformation-specific antibody fragments in the outward-open and inward-open states. In the absence of substrate but in the presence of sodium the transporter is outward-open, illustrating how the binding of substrate closes the extracellular gate through local conformational changes: hinge-bending movements of the extracellular halves of transmembrane domains 1, 2 and 6, together with translation of extracellular loop 4. The inward-open conformation, by contrast, involves large-scale conformational changes, including a reorientation of transmembrane domains 1, 2, 5, 6 and 7, a marked hinge bending of transmembrane domain 1a and occlusion of the extracellular vestibule by extracellular loop 4. These changes close the extracellular gate, open an intracellular vestibule, and largely disrupt the two sodium sites, thus providing a mechanism by which ions and substrate are released to the cytoplasm. The new structures establish a structural framework for the mechanism of neurotransmitter sodium symporters and their modulation by therapeutic and illicit substances.

PubMed: 22230955
DOI: 10.1038/nature10737

実験手法

X-RAY DIFFRACTION (3.099 Å)