Structural analysis and dimerization profile of the SCAN domain of the pluripotency factor Zfp206

Nucleic Acids Res. 2012 Sep 1;40(17):8721-32. doi: 10.1093/nar/gks611. Epub 2012 Jun 26.

Abstract

Zfp206 (also named as Zscan10) belongs to the subfamily of C(2)H(2) zinc finger transcription factors, which is characterized by the N-terminal SCAN domain. The SCAN domain mediates self-association and association between the members of SCAN family transcription factors, but the structural basis and selectivity determinants for complex formation is unknown. Zfp206 is important for maintaining the pluripotency of embryonic stem cells presumably by combinatorial assembly of itself or other SCAN family members on enhancer regions. To gain insights into the folding topology and selectivity determinants for SCAN dimerization, we solved the 1.85 Å crystal structure of the SCAN domain of Zfp206. In vitro binding studies using a panel of 20 SCAN proteins indicate that the SCAN domain Zfp206 can selectively associate with other members of SCAN family transcription factors. Deletion mutations showed that the N-terminal helix 1 is critical for heterodimerization. Double mutations and multiple mutations based on the Zfp206SCAN-Zfp110SCAN model suggested that domain swapped topology is a possible preference for Zfp206SCAN-Zfp110SCAN heterodimer. Together, we demonstrate that the Zfp206SCAN constitutes a protein module that enables C(2)H(2) transcription factor dimerization in a highly selective manner using a domain-swapped interface architecture and identify novel partners for Zfp206 during embryonal development.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Crystallography, X-Ray
  • Dimerization
  • Embryonic Stem Cells / metabolism
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Sequence Alignment
  • Transcription Factors / chemistry*
  • Transcription Factors / metabolism

Substances

  • Transcription Factors
  • ZFP206 protein, mouse

Associated data

  • PDB/4E6S