A novel matrix attachment region DNA binding motif identified using a random phage peptide library

J Biol Chem. 1995 Oct 6;270(40):23239-42. doi: 10.1074/jbc.270.40.23239.

Abstract

SATB1 is a nuclear matrix attachment DNA (MAR)-binding protein which is predominantly expressed in thymocytes. This protein binds to the minor groove specifically recognizing an unusual DNA context exhibited by a specific MAR region with strong base-unpairing propensity. A phage library displaying nonamer random peptides without any built-in structure was used to identify a MAR binding motif of SATB1. One predominant cyclic peptide C1 of CRQNWGLEGC selected by a MAR-affinity column showed 50% identity with a segment in SATB1 (amino acids 355-363). Replacement of the C1 similarity segment in SATB1 by a random amino acid sequence or its truncation resulted in more than 80% reduction in MAR binding. In contrast, replacement of the same SATB1 segment with the C1 peptide restored full MAR binding activity and specificity as the wild-type protein. Single amino acid mutation of the conserved Arg or Glu residue to Ala greatly reduced MAR binding. Taken together our data show that a nine amino acid sequence in SATB1 represents a key MAR binding motif. Phage display may provide a general tool for rapid identification of DNA binding peptide motifs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Bacteriophages / genetics
  • Base Sequence
  • Binding Sites
  • DNA / genetics
  • DNA / metabolism
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Gene Library
  • Humans
  • Matrix Attachment Region Binding Proteins*
  • Molecular Sequence Data
  • Peptides / genetics
  • T-Lymphocytes / metabolism

Substances

  • DNA-Binding Proteins
  • Matrix Attachment Region Binding Proteins
  • Peptides
  • SATB1 protein, human
  • DNA