The conformational switch in 7-transmembrane receptors: the muscarinic receptor paradigm

被引:37
作者
Hulme, EC [1 ]
Lu, ZL [1 ]
Ward, SDC [1 ]
Allman, K [1 ]
Curtis, CAM [1 ]
机构
[1] Natl Inst Med Res, Div Phys Biochem, London NW7 1AA, England
基金
英国医学研究理事会;
关键词
7-transmembrane receptor; G-protein; G-protein coupling pocket; muscarinic receptor; acetylcholine;
D O I
10.1016/S0014-2999(99)00297-6
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The rhodopsin-like superfamily of 7-transmembrane receptors is the largest class of signalling molecules in the mammalian genome. Recently, a combination of mutagenesis, biophysical and modelling studies have suggested a credible model for the alpha-carbon backbone in the transmembrane region of the 7-transmembrane receptors, and have started to reveal the structural basis of the conformational switch from the inactive to the active state. A key feature may be the replacement of a network of radial constraints, centred an transmembrane helix three, which stabilise the inactive ground state of the receptor by a new set of axial interactions which help to stabilise the activated state. Transmembrane helix three may act as a rotary switch in the activation mechanism. (C) 1999 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:247 / 260
页数:14
相关论文
共 84 条
[1]   Light-induced exposure of the cytoplasmic end of transmembrane helix seven in rhodopsin [J].
Abdulaev, NG ;
Ridge, KD .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (22) :12854-12859
[2]   Certain activating mutations within helix 6 of the human luteinizing hormone receptor may be explained by alterations that allow transmembrane regions to activate Gs [J].
Abell, AN ;
McCormick, DJ ;
Segaloff, DL .
MOLECULAR ENDOCRINOLOGY, 1998, 12 (12) :1857-1869
[3]   Transducin-alpha C-terminal peptide binding site consists of C-D and E-F loops of rhodopsin [J].
Acharya, S ;
Saad, Y ;
Karnik, SS .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (10) :6519-6524
[4]   Analysis of zinc binding sites in protein crystal structures [J].
Alberts, IL ;
Nadassy, K ;
Wodak, SJ .
PROTEIN SCIENCE, 1998, 7 (08) :1700-1716
[5]  
Allman K., 1997, Life Sciences, V60, P1177, DOI 10.1016/S0024-3205(97)84326-3
[6]   Structural features and light-dependent changes in the cytoplasmic interhelical E-F loop region of rhodopsin: A site-directed spin-labeling study [J].
Altenbach, C ;
Yang, K ;
Farrens, DL ;
Farahbakhsh, ZT ;
Khorana, HG ;
Hubbell, WL .
BIOCHEMISTRY, 1996, 35 (38) :12470-12478
[7]  
AXELSEN PH, 1994, PROTEIN SCI, V3, P188
[8]   THE PROBABLE ARRANGEMENT OF THE HELICES IN G-PROTEIN-COUPLED RECEPTORS [J].
BALDWIN, JM .
EMBO JOURNAL, 1993, 12 (04) :1693-1703
[9]   THE CONSERVED 7-TRANSMEMBRANE SEQUENCE NP(X)(2,3)Y OF THE G-PROTEIN-COUPLED RECEPTOR SUPERFAMILY REGULATES MULTIPLE PROPERTIES OF THE BETA(2)-ADRENERGIC RECEPTOR [J].
BARAK, LS ;
MENARD, L ;
FERGUSON, SSG ;
COLAPIETRO, AM ;
CARON, MG .
BIOCHEMISTRY, 1995, 34 (47) :15407-15414
[10]   Neurobiology of the Caenorhabditis elegans genome [J].
Bargmann, CI .
SCIENCE, 1998, 282 (5396) :2028-2033