Structure and Function of Steroid Receptor AF1 Transactivation Domains: Induction of Active Conformations

Derek Lavery, Iain Joseph McEwan

Research output: Contribution to journalArticle

118 Citations (Scopus)

Abstract

Steroid hormones are important endocrine signalling molecules controlling reproduction, development, metabolism, salt balance and specialized cellular responses, such as inflammation and immunity. They are lipophilic in character and act by binding to intracellular receptor proteins. These receptors function as ligand-activated transcription factors, switching on or off networks of genes in response to a specific hormone signal. The receptor proteins have a conserved domain organization, comprising a C-terminal LBD (ligand-binding domain), a hinge region, a central DBD (DNA-binding domain) and a highly variable NTD (N-terminal domain). The NTD is structurally flexible and contains surfaces for both activation and repression of gene transcription, and the strength of the transactivation response has been correlated with protein length. Recent evidence supports a structural and functional model for the NTD that involves induced folding, possibly involving alpha-helix structure, in response to protein-protein interactions and structure-stabilizing solutes.

Original languageEnglish
Pages (from-to)449-464
Number of pages15
JournalBiochemical Journal
Volume389
DOIs
Publication statusPublished - 2005

Keywords

  • AF1 transactivation domain
  • allosteric regulation
  • protein-nucleic acid interaction
  • protein-protein interaction
  • post-translational modification
  • secondary structure
  • steroid receptor
  • HUMAN GLUCOCORTICOID-RECEPTOR
  • HUMAN ANDROGEN RECEPTOR
  • HUMAN ESTROGEN-RECEPTOR
  • LIGAND-BINDING DOMAIN
  • HUMAN MINERALOCORTICOID RECEPTOR
  • HUMAN PROGESTERONE-RECEPTORS
  • TRANSCRIPTION FACTOR-TFIIF
  • AMINO-TERMINAL DOMAIN
  • ACTIVATION FUNCTION 1
  • RNA-POLYMERASE-II

Cite this

Structure and Function of Steroid Receptor AF1 Transactivation Domains: Induction of Active Conformations. / Lavery, Derek; McEwan, Iain Joseph.

In: Biochemical Journal, Vol. 389, 2005, p. 449-464.

Research output: Contribution to journalArticle

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