Flexibility and Disorder in Gene Regulation: LacI/GalR and Hox Proteins

J Biol Chem. 2015 Oct 9;290(41):24669-77. doi: 10.1074/jbc.R115.685032. Epub 2015 Sep 4.

Abstract

To modulate transcription, a variety of input signals must be sensed by genetic regulatory proteins. In these proteins, flexibility and disorder are emerging as common themes. Prokaryotic regulators generally have short, flexible segments, whereas eukaryotic regulators have extended regions that lack predicted secondary structure (intrinsic disorder). Two examples illustrate the impact of flexibility and disorder on gene regulation: the prokaryotic LacI/GalR family, with detailed information from studies on LacI, and the eukaryotic family of Hox proteins, with specific insights from investigations of Ultrabithorax (Ubx). The widespread importance of structural disorder in gene regulatory proteins may derive from the need for flexibility in signal response and, particularly in eukaryotes, in protein partner selection.

Keywords: DNA; DNA operator; DNA-binding protein; Hox proteins; LacI/GalR proteins; Ultrabithorax; gene regulation; intrinsic disorder; protein flexibility; repressor protein; transcription factor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Amino Acid Sequence
  • DNA / genetics
  • DNA / metabolism
  • Gene Expression Regulation*
  • Homeodomain Proteins / chemistry*
  • Homeodomain Proteins / metabolism*
  • Humans
  • Lac Repressors / chemistry*
  • Lac Repressors / metabolism*
  • Molecular Sequence Data
  • Repressor Proteins / chemistry*
  • Repressor Proteins / metabolism*

Substances

  • Homeodomain Proteins
  • Lac Repressors
  • Repressor Proteins
  • DNA

Associated data

  • PDB/1A1I
  • PDB/1B8I
  • PDB/1ENH
  • PDB/1LBG
  • PDB/1LBH
  • PDB/1QZ7