A STRUCTURAL ROLE FOR HORMONE IN THE THYROID-HORMONE RECEPTOR

被引:778
作者
WAGNER, RL
APRILETTI, JW
MCGRATH, ME
WEST, BL
BAXTER, JD
FLETTERICK, RJ
机构
[1] UNIV CALIF SAN FRANCISCO, METAB RES UNIT, SAN FRANCISCO, CA 94143 USA
[2] UNIV CALIF SAN FRANCISCO, DEPT MED, SAN FRANCISCO, CA 94143 USA
[3] UNIV CALIF SAN FRANCISCO, DEPT BIOCHEM & BIOPHYS, SAN FRANCISCO, CA 94143 USA
[4] KHEPRI PHARMACEUT INC, San Francisco, CA 94080 USA
关键词
D O I
10.1038/378690a0
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 crystal structure of the rat a, thyroid hormone receptor ligand-binding domain bound with a thyroid hormone agonist reveals that ligand is completely buried within the domain as part of the hydrophobic core. In addition, the carboxy-terminal activation domain forms an amphipathic helix, with its hydrophobic face constituting part of the hormone binding cavity. These observations suggest a structural role for ligand, in establishing the active conformation of the receptor, that is likely to underlie hormonal regulation of gene expression for the nuclear receptors.
引用
收藏
页码:690 / 697
页数:8
相关论文
共 49 条
  • [31] INTERACTION OF THYROID-HORMONE RECEPTOR WITH A CONSERVED TRANSCRIPTIONAL MEDIATOR
    LEE, JW
    RYAN, F
    SWAFFIELD, JC
    JOHNSTON, SA
    MOORE, DD
    [J]. NATURE, 1995, 374 (6517) : 91 - 94
  • [32] MOUSE RETINOID-X RECEPTOR CONTAINS A SEPARABLE LIGAND-BINDING AND TRANSACTIVATION DOMAIN IN ITS E-REGION
    LENG, XH
    BLANCO, J
    TSAI, SY
    OZATO, K
    OMALLEY, BW
    TSAI, MJ
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 1995, 15 (01) : 255 - 263
  • [33] AN ESSENTIAL ROLE OF DOMAIN-D IN THE HORMONE-BINDING ACTIVITY OF HUMAN BETA-1 THYROID-HORMONE NUCLEAR RECEPTOR
    LIN, KH
    PARKISON, C
    MCPHIE, P
    CHENG, SY
    [J]. MOLECULAR ENDOCRINOLOGY, 1991, 5 (04) : 485 - 492
  • [34] CRYSTALLOGRAPHIC ANALYSIS OF THE INTERACTION OF THE GLUCOCORTICOID RECEPTOR WITH DNA
    LUISI, BF
    XU, WX
    OTWINOWSKI, Z
    FREEDMAN, LP
    YAMAMOTO, KR
    SIGLER, PB
    [J]. NATURE, 1991, 352 (6335) : 497 - 505
  • [35] PRELIMINARY CRYSTALLOGRAPHIC STUDIES OF THE LIGAND-BINDING DOMAIN OF THE THYROID-HORMONE RECEPTOR COMPLEXED WITH TRIIODOTHYRONINE
    MCGRATH, ME
    WAGNER, RL
    APRILETTI, JW
    WEST, BL
    RAMALINGAM, V
    BAXTER, JD
    FLETTERICK, RJ
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 1994, 237 (02) : 236 - 239
  • [36] PROTEIN FOLDING AND ASSOCIATION - INSIGHTS FROM THE INTERFACIAL AND THERMODYNAMIC PROPERTIES OF HYDROCARBONS
    NICHOLLS, A
    SHARP, KA
    HONIG, B
    [J]. PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS, 1991, 11 (04) : 281 - 296
  • [37] Otwinowski Z., 1991, ISOMORPHOUS REPLACEM, P80
  • [38] RATINEJAD F, 1995, NATURE, V375, P203
  • [39] THE SYNDROMES OF RESISTANCE TO THYROID-HORMONE
    REFETOFF, S
    WEISS, RE
    USALA, SJ
    [J]. ENDOCRINE REVIEWS, 1993, 14 (03) : 348 - 399
  • [40] THYROID-HORMONE ALTERS INVITRO DNA-BINDING OF MONOMERS AND DIMERS OF THYROID-HORMONE RECEPTORS
    RIBEIRO, RC
    KUSHNER, PJ
    APRILETTI, JW
    WEST, BL
    BAXTER, JD
    [J]. MOLECULAR ENDOCRINOLOGY, 1992, 6 (07) : 1142 - 1152