CRYSTAL-STRUCTURE OF THE RAR-GAMMA LIGAND-BINDING DOMAIN BOUND TO ALL-TRANS-RETINOIC ACID

被引：986

作者：

RENAUD, JP ^{[1
]}

ROCHEL, N ^{[1
]}

RUFF, M ^{[1
]}

VIVAT, V ^{[1
]}

CHAMBON, P ^{[1
]}

GRONEMEYER, H ^{[1
]}

MORAS, D ^{[1
]}

机构：

[1] UNIV STRASBOURG 1,COLL FRANCE,CNRS,INSERM,INST GENET & BIOL MOLEC & CELLULAIRE,F-67404 ILLKIRCH GRAFFENS,FRANCE

来源：

NATURE | 1995年 / 378卷 / 6558期

关键词：

D O I：

10.1038/378681a0

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The 2.0-Angstrom crystal structure of the ligand-binding domain (LED) of the human retinoic acid receptor (RAR)-gamma bound to all-trans retinoic acid reveals the ligand-binding interactions and suggests an electrostatic guidance mechanism. The overall fold is similar to that of the human RXR-alpha apo-LBD, except for the carboxy-terminal part which folds back towards the LED core, contributing to the hydrophobic ligand pocket and 'sealing' its entry site. We propose a 'mouse trap' mechanism whereby a ligand-induced conformational transition repositions the amphipathic alpha-helix of the AF-2 activating domain and forms a transcriptionally active receptor.

引用

页码：681 / 689

页数：9

共 49 条

[1]

ALLENBY G, 1994, J BIOL CHEM, V269, P16689

[2]

[Anonymous], 1994, ACTA CRYSTALLOGR D, V50, P760

[3] CHARACTERIZATION OF THE LIGAND-DEPENDENT TRANSACTIVATION DOMAIN OF THYROID-HORMONE RECEPTOR [J].

BARETTINO, D ;

RUIZ, MDMV ;

STUNNENBERG, HG .

EMBO JOURNAL, 1994, 13 (13) :3039-3049

[4]

BAUR EV, IN PRESS EMBO J

[5] CRYSTAL-STRUCTURE OF THE LIGAND-BINDING DOMAIN OF THE HUMAN NUCLEAR RECEPTOR RXR-ALPHA [J].

BOURGUET, W ;

RUFF, M ;

CHAMBON, P ;

GRONEMEYER, H ;

MORAS, D .

NATURE, 1995, 375 (6530) :377-382

[6] IDENTIFICATION OF A 2ND HUMAN RETINOIC ACID RECEPTOR [J].

BRAND, N ;

PETKOVICH, M ;

KRUST, A ;

CHAMBON, P ;

DETHE, H ;

MARCHIO, A ;

TIOLLAIS, P ;

DEJEAN, A .

NATURE, 1988, 332 (6167) :850-853

[7] FREE R-VALUE - A NOVEL STATISTICAL QUANTITY FOR ASSESSING THE ACCURACY OF CRYSTAL-STRUCTURES [J].

BRUNGER, AT .

NATURE, 1992, 355 (6359) :472-475

[8]

BRUNGER AT, 1992, X PLOR VERSION 3 1

[9] INTERACTION OF PROTEINS WITH TRANSCRIPTIONALLY ACTIVE ESTROGEN-RECEPTORS [J].

CAVAILLES, V ;

DAUVOIS, S ;

DANIELIAN, PS ;

PARKER, MG .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (21) :10009-10013

[10] NUCLEAR FACTOR RIP140 MODULATES TRANSCRIPTIONAL ACTIVATION BY THE ESTROGEN-RECEPTOR [J].

CAVAILLES, V ;

DAUVOIS, S ;

LHORSET, F ;

LOPEZ, G ;

HOARE, S ;

KUSHNER, PJ ;

PARKER, MG .

EMBO JOURNAL, 1995, 14 (15) :3741-3751

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