EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Structural basis for the transport mechanism and cholesterol modulation of the human proline transporter.
ジャーナル・号・ページ	Nat Commun, Vol. 17, Issue 1, Year 2026
掲載日	2026年5月6日
著者	Yue Zhou / Ningqin Wang / Jiaqi Wang / Xinrui Meng / Jing-Xiang Wu /
PubMed 要旨	L-proline, an amino acid, acts as a potent neuromodulator in the central nervous system, with its synaptic concentrations finely regulated by the high-affinity L-proline transporter (PROT). ...L-proline, an amino acid, acts as a potent neuromodulator in the central nervous system, with its synaptic concentrations finely regulated by the high-affinity L-proline transporter (PROT). Dysregulation of PROT function is implicated in neuropsychiatric disorders, yet its regulatory mechanisms remain poorly characterized. Here, we present high-resolution cryo-electron microscopy structures of human PROT in L-proline-free consensus and L-proline-bound states. The L-proline-bound structure reveals an occluded conformation, detailing the coordination of substrate and ions. Strikingly, our L-proline-free consensus structures capture an inward-open conformation with a cholesterol molecule bound directly within the substrate-binding site. Transport kinetics studies demonstrate that partial cholesterol depletion increases PROT's apparent affinity for L-proline, confirming that cholesterol inhibits L-proline uptake. Furthermore, we identify a conformationally sensitive site (CHOL1') present only in the inward-open conformation. This work elucidates PROT's transport cycle and demonstrates how cholesterol directly modulates neurotransmitter uptake, offering potential therapeutic strategies for brain disorders.
リンク	Nat Commun / PubMed:42091899 / PubMed Central
手法	EM (単粒子)
解像度	2.57 - 3.01 Å
構造データ	66096 9wml EMDB-66096, PDB-9wml: Structural mechanism of substrate binding of the human Proline Transporter 手法: EM (単粒子) / 解像度: 2.79 Å 66097 9wmm EMDB-66097, PDB-9wmm: Structure of the cholesterol-bound human proline transporter purified in DDM/CHS buffer 手法: EM (単粒子) / 解像度: 2.8 Å 66098 9wmn EMDB-66098, PDB-9wmn: Structure of the apo-state human proline transporter purified in DDM/CHS buffer 手法: EM (単粒子) / 解像度: 2.91 Å 66099 9wmo EMDB-66099, PDB-9wmo: Structure of the apo-state human proline transporter purified in DDM buffer 手法: EM (単粒子) / 解像度: 3.01 Å 66100 9wmp EMDB-66100, PDB-9wmp: Structure of the cholesterol-bound human proline transporter purified in DDM buffer 手法: EM (単粒子) / 解像度: 2.91 Å 66332 9wx7 EMDB-66332, PDB-9wx7: Structure of the L-proline-free human proline transporter purified in DDM/CHS buffer 手法: EM (単粒子) / 解像度: 2.57 Å 66339 9wx9 EMDB-66339, PDB-9wx9: Structure of the L-proline-free human proline transporter purified in DDM buffer 手法: EM (単粒子) / 解像度: 2.84 Å
化合物	ChemComp-NA: Unknown entry ChemComp-CL: Unknown entry ChemComp-8LJ: (2S)-2,3-dihydro-1H-pyrrole-2-carboxylic acid ChemComp-CLR: CHOLESTEROL ChemComp-Y01: CHOLESTEROL HEMISUCCINATE
由来	homo sapiens (ヒト)
キーワード	TRANSPORT PROTEIN / L-PROLINE / human proline transporter purified / 12 transmembrane helices