Crystal structure of a heterodimeric complex of RAR and RXR ligand-binding domains.

Abstract:

:The crystal structure of a heterodimer between the ligand-binding domains (LBDs) of the human RARalpha bound to a selective antagonist and the constitutively active mouse RXRalphaF318A mutant shows that, pushed by a bulky extension of the ligand, RARalpha helix H12 adopts an antagonist position. The unexpected presence of a fatty acid in the ligand-binding pocket of RXRalpha(F318A is likely to account for its apparent "constitutivity." Specific conformational changes suggest the structural basis of pure and partial antagonism. The RAR-RXR heterodimer interface is similar to that observed in most nuclear receptor (NR) homodimers. A correlative analysis of 3D structures and sequences provides a novel view on dimerization among members of the nuclear receptor superfamily.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Bourguet W,Vivat V,Wurtz JM,Chambon P,Gronemeyer H,Moras D

doi

10.1016/s1097-2765(00)80424-4

subject

Has Abstract

pub_date

2000-02-01 00:00:00

pages

289-98

issue

2

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(00)80424-4

journal_volume

5

pub_type

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