Selective dimerization of a C2H2 zinc finger subfamily.
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.
McCarty
Aaron S
AS
Howard Hughes Medical Institute, Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Kleiger
Gary
G
Eisenberg
David
D
Smale
Stephen T
ST
D000595:Amino Acid Sequence; D000818:Animals; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics; D019281:Dimerization; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics; D006801:Humans; D051740:Ikaros Transcription Factor; D066298:In Vitro Techniques; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009363:Neoplasm Proteins; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics; D012097:Repressor Proteins; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics; D016335:Zinc Fingers / Q000235:genetics
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C497239:IKZF1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C108387:TRPS1 protein, human; D014157:Transcription Factors; C497238:Zfpn1a1 protein, mouse; C061245:hb protein, Drosophila; D051740:Ikaros Transcription Factor