The B-box dominates SAP-1-SRF interactions in the structure of the ternary complex

EMBO J. 2001 Jun 15;20(12):3018-28. doi: 10.1093/emboj/20.12.3018.

Abstract

The serum response element (SRE) is found in several immediate-early gene promoters. This DNA sequence is necessary and sufficient for rapid transcriptional induction of the human c-fos proto-oncogene in response to stimuli external to the cell. Full activation of the SRE requires the cooperative binding of a ternary complex factor (TCF) and serum response factor (SRF) to their specific DNA sites. The X-ray structure of the human SAP-1-SRF-SRE DNA ternary complex was determined (Protein Data Bank code 1hbx). It shows SAP-1 TCF bound to SRF through interactions between the SAP-1 B-box and SRF MADS domain in addition to contacts between their respective DNA-binding motifs. The SAP-1 B-box is part of a flexible linker of which 21 amino acids become ordered upon ternary complex formation. Comparison with a similar region from the yeast MATalpha2-MCM1-DNA complex suggests a common binding motif through which MADS-box proteins may interact with additional factors such as Fli-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • DNA / chemistry*
  • DNA / metabolism
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / metabolism
  • Glycoproteins / chemistry*
  • Glycoproteins / metabolism
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Proteins / chemistry*
  • Nuclear Proteins / metabolism
  • Nucleic Acid Conformation
  • Protein Structure, Secondary
  • Regulatory Sequences, Nucleic Acid
  • Saposins
  • Serum Response Factor
  • Sphingolipid Activator Proteins

Substances

  • DNA-Binding Proteins
  • Glycoproteins
  • Nuclear Proteins
  • PSAP protein, human
  • Saposins
  • Serum Response Factor
  • Sphingolipid Activator Proteins
  • DNA