東華大學圖書館 |

語系: 繁體中文

說明(常見問題)

回圖書館首頁

手機版館藏查詢

登入

回首頁

切換: 標籤 | MARC模式 | ISBD

Structural studies on the ligand sti...

Xu, Rui.

FindBook

Google Book

Amazon

博客來

Structural studies on the ligand stimulation of nicotinic acetylcholine receptor alpha9.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Structural studies on the ligand stimulation of nicotinic acetylcholine receptor alpha9./
作者:	Xu, Rui.
面頁冊數:	152 p.
附註:	Adviser: Wayne A. Hendrickson.
Contained By:	Dissertation Abstracts International68-09B.
標題:	Biology, Neuroscience. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3285206
ISBN:	9780549273172

Structural studies on the ligand stimulation of nicotinic acetylcholine receptor alpha9.
Xu, Rui.

Structural studies on the ligand stimulation of nicotinic acetylcholine receptor alpha9. - 152 p.

Adviser: Wayne A. Hendrickson.

Thesis (Ph.D.)--Columbia University, 2007.

Nicotinic acetylcholine receptor (nAChR) is a member of the Cys-loop ligand-gated ion channel (LGIC) superfamily, which also includes 5-hydroxytryptamine (5-HT3), gamma-aminobutyric acid (GABA) and glycine receptors. LGICs function on a timescale of milliseconds upon binding of neurotransmitters and mediate fast synaptic transmission in the nervous system. nAChRs are important therapeutic drug targets for treatments of nicotine addiction and multiple neurological diseases including schizophrenia, Alzheimer's disease and Parkinson's disease. They are pentameric complexes formed by homologous subunits with a selective ion pore in the centre and each subunit comprises a large N-terminal extracellular ligand-binding domain followed by a channel forming transmembrane domain and an intracellular domain. The ligand-binding domain of nAChR harbours neurotransmitter-binding site and is the key for the understanding of ligand induced channel gating. In this thesis, I report the crystal structures of chicken alpha9 extracellular ligand-binding domain in complex with multiple nicotinic antagonists and agonists. The alpha9 protomer displays a beta rich structure with conserved major determinants for receptor-ligand interactions. Comparison of the structures reveals that agonist binding induces contraction of the ligand binding site and domain bending of the ligand-binding domain. Based on this finding, we propose a "twisted contraction" mechanism of the ligand-binding domain complex in receptor during gating. Unique structural motifs, including the signature Cys-loop and an electrostatic triad mediated by Arg210, Glu47, Asp140 and Glu177, are essential for signal propagation from ligand binding to channel opening. The information provided by the structures is essential for the exploration of the receptor gating mechanism and provides a great start point for homology modelling and drug design of the Cys-loop LGIC receptor superfamily.

ISBN: 9780549273172Subjects--Topical Terms:

1017680
Biology, Neuroscience.

Structural studies on the ligand stimulation of nicotinic acetylcholine receptor alpha9.
LDR:02875nam 2200289 a 45 001 938953
005 20110512
008 110512s2007 eng d
020 $a 9780549273172
035 $a (UMI)AAI3285206
035 $a AAI3285206
040 $a UMI $c UMI
100 1 $a Xu, Rui. $3 1262927
245 1 0 $a Structural studies on the ligand stimulation of nicotinic acetylcholine receptor alpha9.
300 $a 152 p.
500 $a Adviser: Wayne A. Hendrickson.
500 $a Source: Dissertation Abstracts International, Volume: 68-09, Section: B, page: 5794.
502 $a Thesis (Ph.D.)--Columbia University, 2007.
520 $a Nicotinic acetylcholine receptor (nAChR) is a member of the Cys-loop ligand-gated ion channel (LGIC) superfamily, which also includes 5-hydroxytryptamine (5-HT3), gamma-aminobutyric acid (GABA) and glycine receptors. LGICs function on a timescale of milliseconds upon binding of neurotransmitters and mediate fast synaptic transmission in the nervous system. nAChRs are important therapeutic drug targets for treatments of nicotine addiction and multiple neurological diseases including schizophrenia, Alzheimer's disease and Parkinson's disease. They are pentameric complexes formed by homologous subunits with a selective ion pore in the centre and each subunit comprises a large N-terminal extracellular ligand-binding domain followed by a channel forming transmembrane domain and an intracellular domain. The ligand-binding domain of nAChR harbours neurotransmitter-binding site and is the key for the understanding of ligand induced channel gating. In this thesis, I report the crystal structures of chicken alpha9 extracellular ligand-binding domain in complex with multiple nicotinic antagonists and agonists. The alpha9 protomer displays a beta rich structure with conserved major determinants for receptor-ligand interactions. Comparison of the structures reveals that agonist binding induces contraction of the ligand binding site and domain bending of the ligand-binding domain. Based on this finding, we propose a "twisted contraction" mechanism of the ligand-binding domain complex in receptor during gating. Unique structural motifs, including the signature Cys-loop and an electrostatic triad mediated by Arg210, Glu47, Asp140 and Glu177, are essential for signal propagation from ligand binding to channel opening. The information provided by the structures is essential for the exploration of the receptor gating mechanism and provides a great start point for homology modelling and drug design of the Cys-loop LGIC receptor superfamily.
590 $a School code: 0054.
650 4 $a Biology, Neuroscience. $3 1017680
650 4 $a Biophysics, General. $3 1019105
650 4 $a Health Sciences, Pharmacology. $3 1017717
690 $a 0317
690 $a 0419
690 $a 0786
710 2 0 $a Columbia University. $3 571054
773 0 $t Dissertation Abstracts International $g 68-09B.
790 $a 0054
790 1 0 $a Hendrickson, Wayne A., $e advisor
791 $a Ph.D.
792 $a 2007
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3285206