Selective dimerization of a C2H2 zinc finger subfamily

Mol Cell. 2003 Feb;11(2):459-70. doi: 10.1016/s1097-2765(03)00043-1.

Abstract

The C2H2 zinc finger is the most prevalent protein motif in the mammalian proteome. Two C2H2 fingers in Ikaros are dedicated to homotypic interactions between family members. We show here that these fingers comprise a bona fide dimerization domain. Dimerization is highly selective, however, as homologous domains from the TRPS-1 and Drosophila Hunchback proteins support homodimerization, but not heterodimerization with Ikaros. Ikaros-Hunchback selectivity is determined by 11 residues concentrated within the alpha-helical regions typically involved in base recognition. Preferential homodimerization of one chimeric protein predicts a parallel dimer interface and establishes the feasibility of creating novel dimer specificities. These results demonstrate that the C2H2 motif provides a versatile platform for both sequence-specific protein-nucleic acid interactions and highly specific dimerization.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • Dimerization
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / genetics
  • Humans
  • Ikaros Transcription Factor
  • In Vitro Techniques
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Neoplasm Proteins*
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / genetics
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Sequence Homology, Amino Acid
  • Transcription Factors / chemistry*
  • Transcription Factors / genetics
  • Zinc Fingers* / genetics

Substances

  • DNA-Binding Proteins
  • Drosophila Proteins
  • IKZF1 protein, human
  • Neoplasm Proteins
  • Nuclear Proteins
  • Recombinant Fusion Proteins
  • TRPS1 protein, human
  • Transcription Factors
  • Zfpn1a1 protein, mouse
  • hb protein, Drosophila
  • Ikaros Transcription Factor