Sticky fingers: zinc-fingers as protein-recognition motifs.

Zinc-fingers (ZnFs) are extremely abundant in higher eukaryotes. Once considered to function exclusively as sequence-specific DNA-binding motifs, ZnFs are now known to have additional activities such as the recognition of RNA and other proteins. Here we discuss recent advances in our understanding of ZnFs as specific modules for protein recognition. Structural studies of ZnF complexes reveal considerable diversity in terms of protein partners, binding modes and affinities, and highlight the often underestimated versatility of ZnF structure and function. An appreciation of the structural features of ZnF-protein interactions will contribute to our ability to engineer and to use ZnFs with tailored protein-binding properties.

[1]  J. Qin,et al.  Molecular Dissection of PINCH-1 Reveals a Mechanism of Coupling and Uncoupling of Cell Shape Modulation and Survival* , 2005, Journal of Biological Chemistry.

[2]  Somasekar Seshagiri,et al.  De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-κB signalling , 2004, Nature.

[3]  A. Cashmore,et al.  HAT3.1, a novel Arabidopsis homeodomain protein containing a conserved cysteine-rich region. , 1993, The Plant journal : for cell and molecular biology.

[4]  J. Mackay,et al.  Zinc fingers as protein recognition motifs: structural basis for the GATA-1/friend of GATA interaction. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[5]  Merlin Crossley,et al.  Molecular Analysis of the Interaction between the Hematopoietic Master Transcription Factors GATA-1 and PU.1* , 2006, Journal of Biological Chemistry.

[6]  H. Horvitz,et al.  Novel cysteine-rich motif and homeodomain in the product of the Caenorhabditis elegans cell lineage gene lin-II , 1990, Nature.

[7]  S. Orkin,et al.  CREB-binding protein cooperates with transcription factor GATA-1 and is required for erythroid differentiation. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[8]  Peer Bork,et al.  SMART 5: domains in the context of genomes and networks , 2005, Nucleic Acids Res..

[9]  Levon M. Khachigian,et al.  Protein-Protein Interaction between Fli-1 and GATA-1 Mediates Synergistic Expression of Megakaryocyte-Specific Genes through Cooperative DNA Binding , 2003, Molecular and Cellular Biology.

[10]  Yi Zhang,et al.  Structure of a Bmi-1-Ring1B Polycomb Group Ubiquitin Ligase Complex* , 2006, Journal of Biological Chemistry.

[11]  J. Mackay,et al.  Pentaprobe: a comprehensive sequence for the one-step detection of DNA-binding activities. , 2003, Nucleic acids research.

[12]  M. R. Adams,et al.  Comparative genomics of the eukaryotes. , 2000, Science.

[13]  J. Bonifacino,et al.  Structural basis for ubiquitin recognition and autoubiquitination by Rabex-5 , 2006, Nature Structural &Molecular Biology.

[14]  Scot A. Wolfe,et al.  DNA RECOGNITION BY Cys 2 His 2 ZINC FINGER PROTEINS , 2000 .

[15]  S. Orkin,et al.  Transforming Acidic Coiled-coil Protein 3 (TACC3) Controls Friend of GATA-1 (FOG-1) Subcellular Localization and Regulates the Association between GATA-1 and FOG-1 during Hematopoiesis* , 2004, Journal of Biological Chemistry.

[16]  J. Inoue,et al.  Transcriptional activity of testis-determining factor SRY is modulated by the Wilms’ tumor 1 gene product, WT1 , 2003, Oncogene.

[17]  G. Warren,et al.  Direct binding of ubiquitin conjugates by the mammalian p97 adaptor complexes, p47 and Ufd1–Npl4 , 2002, The EMBO journal.

[18]  Scott D Emr,et al.  Ubiquitin interactions of NZF zinc fingers , 2004, The EMBO journal.

[19]  J. Mackay,et al.  Zinc fingers are sticking together. , 1998, Trends in biochemical sciences.

[20]  J. Qin,et al.  Structure of an ultraweak protein-protein complex and its crucial role in regulation of cell morphology and motility. , 2005, Molecular cell.

[21]  T. Rapoport,et al.  Retro-translocation of proteins from the endoplasmic reticulum into the cytosol , 2002, Nature Reviews Molecular Cell Biology.

[22]  A. Weissman Ubiquitin and proteasomes: Themes and variations on ubiquitylation , 2001, Nature Reviews Molecular Cell Biology.

[23]  M. Beckerle,et al.  The LIM domain: from the cytoskeleton to the nucleus , 2004, Nature Reviews Molecular Cell Biology.

[24]  A Klug,et al.  Repetitive zinc‐binding domains in the protein transcription factor IIIA from Xenopus oocytes. , 1985, The EMBO journal.

[25]  Zhijian J. Chen,et al.  TAB2 and TAB3 activate the NF-kappaB pathway through binding to polyubiquitin chains. , 2004, Molecular cell.

[26]  Dana Carroll,et al.  Enhancing Gene Targeting with Designed Zinc Finger Nucleases , 2003, Science.

[27]  D. Eisenberg,et al.  Selective dimerization of a C2H2 zinc finger subfamily. , 2003, Molecular cell.

[28]  W. Sundquist,et al.  Structure and Ubiquitin Interactions of the Conserved Zinc Finger Domain of Npl4* , 2003, Journal of Biological Chemistry.

[29]  A. Leutz,et al.  The Conserved Mynd Domain of BS69 Binds Cellular and Oncoviral Proteins through a Common PXLXP Motif* , 2002, The Journal of Biological Chemistry.

[30]  J. Visvader,et al.  Structural basis for the recognition of ldb1 by the N‐terminal LIM domains of LMO2 and LMO4 , 2003, The EMBO journal.

[31]  J. Visvader,et al.  A Classic Zinc Finger from Friend of GATA Mediates an Interaction with the Coiled-coil of Transforming Acidic Coiled-coil 3* , 2004, Journal of Biological Chemistry.

[32]  C. Pabo,et al.  DNA recognition by Cys2His2 zinc finger proteins. , 2000, Annual review of biophysics and biomolecular structure.

[33]  S. Bhattacharya,et al.  An essential role for p300/CBP in the cellular response to hypoxia. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[34]  R. Y. Tsai,et al.  Identification of DNA Recognition Sequences and Protein Interaction Domains of the Multiple-Zn-Finger Protein Roaz , 1998, Molecular and Cellular Biology.

[35]  E. Querfurth,et al.  GATA-1 interacts with the myeloid PU.1 transcription factor and represses PU.1-dependent transcription. , 2000, Blood.

[36]  Xiaodong Cheng,et al.  The Ubiquitin Binding Domain ZnF UBP Recognizes the C-Terminal Diglycine Motif of Unanchored Ubiquitin , 2006, Cell.

[37]  R. Boelens,et al.  Identification of a ubiquitin–protein ligase subunit within the CCR4–NOT transcription repressor complex , 2002, The EMBO journal.

[38]  Thomas A. Milne,et al.  A PHD finger of NURF couples histone H3 lysine 4 trimethylation with chromatin remodelling , 2006, Nature.

[39]  Aaron Klug,et al.  Crystal structure of a zinc-finger–RNA complex reveals two modes of molecular recognition , 2003, Nature.

[40]  P. Gottlieb,et al.  m-Bop, a Repressor Protein Essential for Cardiogenesis, Interacts with skNAC, a Heart- and Muscle-specific Transcription Factor* , 2002, The Journal of Biological Chemistry.

[41]  S. Elledge,et al.  Structure of the Cul1–Rbx1–Skp1–F boxSkp2 SCF ubiquitin ligase complex , 2002, Nature.

[42]  D. Speicher,et al.  Reconstitution of the KRAB-KAP-1 repressor complex: a model system for defining the molecular anatomy of RING-B box-coiled-coil domain-mediated protein-protein interactions. , 2000, Journal of molecular biology.

[43]  M S Boguski,et al.  The A20 cDNA induced by tumor necrosis factor alpha encodes a novel type of zinc finger protein. , 1990, The Journal of biological chemistry.

[44]  J. Visvader,et al.  Tandem LIM domains provide synergistic binding in the LMO4:Ldb1 complex , 2004, The EMBO journal.

[45]  J. Mackay,et al.  The N-terminal Zinc Finger of the Erythroid Transcription Factor GATA-1 Binds GATC Motifs in DNA* , 2001, The Journal of Biological Chemistry.

[46]  A. Vėlyvis,et al.  Solution Structure of the Focal Adhesion Adaptor PINCH LIM1 Domain and Characterization of Its Interaction with the Integrin-linked Kinase Ankyrin Repeat Domain* , 2001, The Journal of Biological Chemistry.

[47]  W. McGinnis,et al.  DEAF‐1, a novel protein that binds an essential region in a Deformed response element. , 1996, The EMBO journal.

[48]  B. Thompson,et al.  Pygopus Residues Required for its Binding to Legless Are Critical for Transcription and Development* , 2004, Journal of Biological Chemistry.

[49]  B. Morgan,et al.  Helios, a novel dimerization partner of Ikaros expressed in the earliest hematopoietic progenitors , 1998, Current Biology.

[50]  R. Lovering,et al.  Identification and preliminary characterization of a protein motif related to the zinc finger. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[51]  Gerhard Wagner,et al.  Structural basis for negative regulation of hypoxia-inducible factor-1α by CITED2 , 2003, Nature Structural Biology.

[52]  Rolf Boelens,et al.  Structural model of the UbcH5B/CNOT4 complex revealed by combining NMR, mutagenesis, and docking approaches. , 2004, Structure.

[53]  Peter E Wright,et al.  Interaction of the TAZ1 Domain of the CREB-Binding Protein with the Activation Domain of CITED2 , 2004, Journal of Biological Chemistry.

[54]  Ping Wang,et al.  Structure of a c-Cbl–UbcH7 Complex RING Domain Function in Ubiquitin-Protein Ligases , 2000, Cell.

[55]  D. Gell,et al.  Engineering a protein scaffold from a PHD finger. , 2003, Structure.

[56]  T. Hall,et al.  Multiple modes of RNA recognition by zinc finger proteins. , 2005, Current opinion in structural biology.

[57]  A. G. Murachelli,et al.  Crystal Structure of the Ubiquitin Binding Domains of Rabex-5 Reveals Two Modes of Interaction with Ubiquitin , 2006, Cell.

[58]  S. Orkin,et al.  Failure of megakaryopoiesis and arrested erythropoiesis in mice lacking the GATA-1 transcriptional cofactor FOG. , 1998, Genes & development.

[59]  M. Bycroft,et al.  Solution Structure of the Kaposi's Sarcoma-associated Herpesvirus K3 N-terminal Domain Reveals a Novel E2-binding C4HC3-type RING Domain* , 2004, Journal of Biological Chemistry.

[60]  C. Ponting,et al.  ZZ and TAZ: new putative zinc fingers in dystrophin and other proteins. , 1996, Trends in biochemical sciences.

[61]  J. Bonifacino,et al.  The Rab5 Guanine Nucleotide Exchange Factor Rabex-5 Binds Ubiquitin (Ub) and Functions as a Ub Ligase through an Atypical Ub-interacting Motif and a Zinc Finger Domain* , 2006, Journal of Biological Chemistry.

[62]  B. Morris,et al.  The Structure of the Zinc Finger Domain from Human Splicing Factor ZNF265 Fold* , 2003, Journal of Biological Chemistry.

[63]  J. Mackay,et al.  The C-terminal Domain of Eos Forms a High Order Complex in Solution* , 2003, Journal of Biological Chemistry.

[64]  S. Khorasanizadeh,et al.  Double chromodomains cooperate to recognize the methylated histone H3 tail , 2005, Nature.

[65]  D. Case,et al.  Induced fit and "lock and key" recognition of 5S RNA by zinc fingers of transcription factor IIIA. , 2006, Journal of molecular biology.

[66]  S. Orkin,et al.  Functional synergy and physical interactions of the erythroid transcription factor GATA-1 with the Krüppel family proteins Sp1 and EKLF , 1995, Molecular and cellular biology.

[67]  J. Mackay,et al.  Transcriptional cofactors of the FOG family interact with GATA proteins by means of multiple zinc fingers , 1999, The EMBO journal.

[68]  Raymond S Brown,et al.  Zinc finger proteins: getting a grip on RNA. , 2005, Current opinion in structural biology.

[69]  V. Verkhusha,et al.  Molecular mechanism of histone H3K4me3 recognition by plant homeodomain of ING2 , 2006, Nature.

[70]  I. Garkavtsev,et al.  The candidate tumour suppressor p33ING1cooperates with p53 in cell growth control , 1998, Nature.

[71]  Oliver Weichenrieder,et al.  Structure and E3‐ligase activity of the Ring–Ring complex of Polycomb proteins Bmi1 and Ring1b , 2006, The EMBO journal.

[72]  Michael Carey,et al.  DNA recognition by GAL4: structure of a protein-DNA complex , 1992, Nature.

[73]  M. Bottomley,et al.  Structure and functional analysis of the MYND domain. , 2006, Journal of molecular biology.

[74]  A M Gronenborn,et al.  NMR structure of a specific DNA complex of Zn-containing DNA binding domain of GATA-1. , 1993, Science.

[75]  G. Blobel CREB-binding protein and p300: molecular integrators of hematopoietic transcription. , 2000, Blood.

[76]  Anjanabha Saha,et al.  ING2 PHD domain links histone H3 lysine 4 methylation to active gene repression , 2006, Nature.

[77]  A. Kentsis,et al.  PML RING suppresses oncogenic transformation by reducing the affinity of eIF4E for mRNA , 2001, The EMBO journal.

[78]  D. Livingston,et al.  Structural basis for recruitment of CBP/p300 by hypoxia-inducible factor-1α , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[79]  H. Dyson,et al.  Structural basis for Hif-1α/CBP recognition in the cellular hypoxic response , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[80]  D. Patel,et al.  Molecular basis for site-specific read-out of histone H3K4me3 by the BPTF PHD finger of NURF , 2006, Nature.

[81]  E. Koonin,et al.  Scores of RINGS but No PHDs in Ubiquitin Signaling , 2003, Cell cycle.