title: A classic zinc finger from friend of GATA mediates an interaction with the coiled-coil of transforming acidic coiled-coil 3.
abstract: Classic zinc finger domains (cZFs) consist of a beta-hairpin followed by an alpha-helix. They are among the most abundant of all protein domains and are often found in tandem arrays in DNA-binding proteins, with each finger contributing an alpha-helix to effect sequence-specific DNA recognition. Lone cZFs, not found in tandem arrays, have been postulated to function in protein interactions. We have studied the transcriptional co-regulator Friend of GATA (FOG), which contains nine zinc fingers. We have discovered that the third cZF of FOG contacts a coiled-coil domain in the centrosomal protein transforming acidic coiled-coil 3 (TACC3). Although FOG-ZF3 exhibited low solubility, we have used a combination of mutational mapping and protein engineering to generate a derivative that was suitable for in vitro and structural analysis. We report that the alpha-helix of FOG-ZF3 recognizes a C-terminal portion of the TACC3 coiled-coil. Remarkably, the alpha-helical surface utilized by FOG-ZF3 is the same surface responsible for the well established sequence-specific DNA-binding properties of many other cZFs. Our data demonstrate the versatility of cZFs and have implications for the analysis of many as yet uncharacterized cZF proteins.
authors.affiliation: School of Molecular and Microbial Biosciences, G08, University of Sydney, NSW 2006, Australia.
authors.forename: Raina J Y
authors.initials: RJ
authors.lastname: Simpson
authors.forename: Stella Hoi
authors.initials: SH
authors.lastname: Yi Lee
authors.forename: Natalie
authors.initials: N
authors.lastname: Bartle
authors.forename: Eleanor Y
authors.initials: EY
authors.lastname: Sum
authors.forename: Jane E
authors.initials: JE
authors.lastname: Visvader
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Matthews
authors.forename: Joel P
authors.initials: JP
authors.lastname: Mackay
authors.forename: Merlin
authors.initials: M
authors.lastname: Crossley
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D019281:Dimerization; D005326:Fetal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012995:Solubility; D014157:Transcription Factors; D016335:Zinc Fingers / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D005326:Fetal Proteins; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; C418485:TACC3 protein, mouse; D014157:Transcription Factors; C498432:ZFPM1 protein, human; C107310:Zfpm1 protein, mouse