Zinc finger structures are as diverse as their functions. Zinc fingers are structurally diverse and exhibit a wide range of functions, from dna or rnabinding to proteinprotein interactions and membrane association. Even though the cchh zinc finger motif has been found to be one of the most ubiquitous. The crystal structure of a two zincfinger peptide reveals an. In maize, dof1 mnb1a is constitutively expressed in leaves, stems, and. Blast analysis revealed that the zinc finger protein is homologous to an mrna splicing. After the discovery of the zinc finger motif, patterns of potential zinc ligands have. These proteins harbor a highly conserved domain, in which a zinc ion is surrounded by cysteine cys andor histidine his residues to stabilize their threedimensional structure, comprising a twostranded antiparallel beta sheets and a helix liu et al. The cys 2his 2 zinc finger is the most widely occurring dnabinding motif. Two types of zinc fingers are required for dimerization of. Dec 16, 2015 zinc fingers very common in eukaryotes there are at least six different versions of the zinc finger cys2his2 finger comprises a series of 12 or so amino acids, including two cysteines and two histidines. Murawska centre for systems chemistry, stratingh institute for.
The zinc finger binds a zinc ion in order to stabilize its threedimensional structure consisting of a twostranded antiparallel. Atc3h17, a nontandem ccch zinc finger protein, functions. Dnabinding motif found in eukaryotic transcriptional factors. Atzp1 is a typical c2h2type zinc finger protein containing an ear motif. Zfps are divided into many families on the basis of the conserved zinc finger motif andor other notable.
The genome of oryza sativa codes for 189 c 2 h 2 zinc finger transcription factors, which possess two main types of zinc fingers named c and q. The cys 2his 2 zincfinger is the most widely occurring dnabinding motif. Pdf zincfinger proteins znfs are one of the most abundant groups of proteins and have a wide range of molecular functions. Consensus sequence 2 cys held in beta sheet and 2 his in alpha helix tetrahedrally coordinated to zn ion.
Zincfinger proteins znfs are one of the most abundant groups of proteins and have a wide range of molecular functions. Variations of the c2h2 zinc finger motif in the yeast genome. Structures have recently been reported for many new zinc finger domains with novel topologies, providing important insights into structurefunction relationships. We have taken a comprehensive approach to the generation of novel dna binding zinc finger domains of defined specificity. Each zinc finger typically binds a 3nt target sequence, and it is possible to engineer zinc finger arrays zfas that recognize extended dna sequences by linking together individual zinc fingers.
It should be noted that both c96 and c106 are parts of the ccch central motif. Engineering zinc finger dnabinding specificity the cys2his2 zinc finger domain represents the most common dnabinding motif in eukaryotes and the second most frequently encoded protein domain in the human genome46. Zinc finger tools provides tools for selecting zinc finger protein zfp target sites and for designing the proteins that will target them. The zincfinger domain is one of the most frequently utilized dnabinding motif found in eukaryotic transcriptional factors. The gap function required an intact zinc finger and additional amino.
The sp1 peptides were folded into functional zinc fingers using zinc chloride. This motif can be repeated many times in a dna binding protein, with each finger folding independently. Conserved cysteine and histidine residues in the putative. Here, we show that the c2h2type zinc finger protein named zinc finger protein1 atzp1, which contains an erfassociated amphiphilic repression ear motif. The influenza virus matrix protein m1 possesses a cysteine and histidine cchh motif in the helix 9 h9 and adjacent region 148 catceqiadsqhrsh 162. Dof is a novel family of plant proteins that share a unique and highly conserved dna binding domain with one c2c2 zinc finger motif. Zinc finger antiviral protein zap is a host antiviral factor that specifically restricts a wide range of viruses. Zinc finger nucleases are useful to manipulate the genomes of many plants and animals. Genomewide identification of c2h2 zincfinger genes and. Pdf snitrosation on zinc finger motif of parp1 as a. If the zinc finger domains are perfectly specific for their intended target site then even a pair of 3 finger zfns that recognize a total of 18 basepairs can, in theory, target a single locus in a mammalian genome. Zinc fingers very common in eukaryotes there are at least six different versions of the zinc finger cys2his2 finger comprises a series of 12 or so amino acids, including two cysteines and two histidines. Zinc finger protein glis1, which has five tandem zinc finger motifs and is a member of the gli and zic family, has a high degree of homology across species ruppert et al. Zinc finger proteins znfs are one of the most abundant groups of proteins and have a wide range of molecular functions.
Type c2h2 zinc fingers bind a variety of substrates, specific sequences in the doublestranded dna counting among them. This enormous contribution of zinc domains and motifs with various metal affinities encourages. An archetypal member of this family is zif268, also known as egr1, which is a transcriptional regulator initially found in mice. Hyonemyong eun, in enzymology primer for recombinant dna technology, 1996 ii zinc finger motif. The atzp1 gene contains a 615bp coding sequence including the stop codon encoding a 22kd protein with 204 amino acids. It should be noted that both c96 and c106 are parts of the ccch central motif of zf2, highlighting the. Introduction the zinc finger motif reprents an important class of dnarna binding proteins in eukaryotes i3. Involvement of maize dof zinc finger proteins in tissue.
Nov, 2017 zinc finger proteins znfs are one of the most abundant groups of proteins and have a wide range of molecular functions. Cys2his2like fold group c2h2type zinc finger proteins promote root hair growth and development by regulating their target genes. Oct 18, 20 however, in the current study, the point mutation in the zinc finger motif of the ehd2rid1osid1 protein in the ghd10 plants conferred obvious advantages to yield formation traits, including increased plant height, panicle length, primary branch number and number of spikelets per panicle, compared with the wild type and three other allelic. Crystal structure of a zincfingerrna complex reveals two.
The zinc finger proteins zfps are one of the largest protein families in plants. Interspecific comparison of drosophila serendipity delta and beta. Pentatricopeptide proteins are known to bind to ciselements near c targets of editing and. The role of zinc finger protein in rnai interference in. Engineered zinc finger proteins have proven to be valuable tools for gene regulation and genome modification because they target specific sites in a. Pdf a zinc finger motifcontaining protein is essential. Zinc finger motif definition of zinc finger motif by the. Originally coined to describe the finger like appearance of a hypothesized structure from xenopus laevis transcription factor iiia, the zinc finger name has now come to encompass a wide variety of differing protein structures.
Coordinate bonds between the zinc atom and neighbouring amino acid sidechains. Pdf zincfinger proteins in health and disease researchgate. The c8 motif, currently formulated by us as cx 2cx 10. The simplicity of the zinc finger structure, and of its interaction with dna, is a very striking feature of this protein domain. Model of interaction of zinc finger protein with dna 1 zinc finger proteins above structure of the first zinc finger of zif268. Highly conserved hydrophobic residues from the ahelix and betasheets help to stabilize the zinc finger motif. Pdf a zinc finger motifcontaining protein is essential for. By arranging two cysteines and two histidines close to each other in a chain, a pro tein can grab a zinc ion and fold tightly around it. Ppt model of interaction of zinc finger protein with dna. Given the wide variety of zinc finger domains, znfs are able to. A nuclear pore complex protein that contains zinc finger motifs. Here, we identified a novel ccchtandem zinc finger. In each finger, two cysteine residues on the beta sheet and two histidine residues on the.
Zinc fingers are a large and diverse protein family classified into several different types, including c2h2, c2c2, c2hc, c2c2c2c2, c2hcc2c2 and ccch, based on the number and order of cysteine and histidine residues bound to zinc ions in the secondary structure of the finger. A single zinc finger does not bind very tightly and can only recognize 2 or 3 base pairs. The zinc finger is one of the most important dnabinding motifs found first in tfiiia and subsequently. Proteins containing zinc finger domains were found to play important roles in eukaryotic cells regulating different signal transduction pathways and controlling processes, such as development and programmed cell death. This modular approach is so appealing that researchers are currently trying to design artificial zinc. Zinc finger residues at 3 dnacontacting positions labeled. A point mutation in the zinc finger motif of rid1ehd2osid1 protein leads to outstanding yieldrelated traits in japonica. Oct 12, 2016 in zinc finger proteins, for example, a zinc ion is complexed in a zinc finger motif through four invariant cysteine andor histidine residues to form a stable structure and conformation, which.
The zinc finger is a common structural motif in many protein dna binding domains. Arabidopsis cys2his2type zincfinger proteins function. A complementary dna encoding the arf1 gap was cloned from rat liver and predicts a protein with a zinc finger motif near the amino terminus. Symbol zn a bluishwhite, lustrous metallic element that is brittle at room temperature but malleable with heating. Ring finger motif of arabidopsis thaliana cop1 defines a new class of zinc. The zinc finger motif reprents an important class of dnarna binding proteins in eukaryotes i3. But when several are strung together, the group binds more tightly and can read longer dna sequences. Zinc finger proteins znfs, such as znf208, bind dna and, through this binding, regulate gene transcription. The cchh motif has been proposed as a putative zinc finger motif and zinc binding activity has been implicated in virus uncoating as well as transcription inhibition and mrna regulation. Unlike the c2h2 motif, where the zinc finger is repeated many times, the gag knuckles are mostly found as two conserved domains separated by a small linker region 44. Jan 12, 2008 the zinc finger domain enables different proteins to interact with or bind dna, rna, or other proteins, and is present in the proteomes of many different organisms.
Genomewide identification of c 2 h 2 zincfinger gene family. After the discovery of the zinc finger motif, patterns of potential zinc ligands have been found in several other proteins, some of which also bind to dna. Improving selectivity of dnarna binding zinc finger using. The atzp1 protein contains one typical c2h2type zinc finger domain between amino acids 46 and 68 and the conserved sequence qalggh inside the zinc finger. The dnabinding region was altered in two places to enable the folded zinc finger. Zinc finger protein motif that forms a compact globular structure that coordinates one or more zn ions. These zfps can be fused with effector domains that confer transcriptional activation or repression activity. Snitrosation on zinc finger motif of parp1 as a mechanism of dna repair inhibition by arsenite. In our experiments we used one of the three zinc finger motifs of the sp1 zinc finger as a template for our chemically synthesized zinc finger probes, which were of the c2h2 type figure 1. Protein kinase c in oncogenic transformation and cell polarity. Choose from different sets of zinc finger motif flashcards on quizlet. Jun 29, 2005 two zinc finger probes of the sp1 motif were chemically synthesized and modified with a dy633 fluorophore. The zinc finger is one of the most important dnabinding motifs found first in tfiiia and subsequently in various other proteins including transcription factors such as sp1 gcbox binding protein, gli human glioblastoma protein, zif268, and a subfamily of nuclear hormone receptors.
The first structure of a zincfingerdna complex revealed a fairly simple mechanism for dna recognition 4. Zinc finger protein 208 is a protein that in humans is encoded by the znf208 gene function. A laboratory manual, second edition cold spring harbor, new york. The addressable dsdnas were immobilized on optical fibres, and the kinetics and binding rates of the artificial zinc finger probes were measured by a. Based on different dna binding motifs, transcription factors can be majorly categorized into classical zinc fingers 6, homeodomains 7, and. Author summary meiosis comprises two successive cell divisions after a single s phase, generating four haploid products.
Most znfs contain conserved c2h2 motifs and are classified as kruppeltype zinc fingers. Oct 15, 2011 the zinc finger is a common structural motif in many protein dna binding domains. In arabidopsis, over 600 genomicallyencoded cs are modified to us in organelle transcripts, altering the encoded amino acids and creating stop and start codons. Molecular mechanism of rna recognition by zincfinger. Zfns are also used to create a new generation of genetic disease models called isogenic human disease models. Ccch zinc finger proteins are characterized by a zinc finger motif consisting of three cysteines and one histidine coordinated by a zinc cation and have been identified in arabidopsis, rice and other plant species 2022. Zincfinger proteins in health and disease cell death. Zap selectively binds to cgdinucleotideenriched rna sequences and recruits multiple rna degradation machines to degrade target viral rna. The most straightforward method to generate new zinc finger arrays is to combine smaller zinc finger. Author summary transcripts encoding chloroplast and mitochondrial proteins of flowering plants are profoundly affected by rna editing. Hydrolysis of guanosine triphosphate gtp by the small guanosine triphosphatase gtpase adenosine diphosphate ribosylation factor1 arf1 depends on a gtpaseactivating protein gap. The arabidopsis jagged gene encodes a zinc finger protein. A grich motif in the lncrna braveheart interacts with a zinc. A zinc finger motifcontaining protein is essential for.
Zinc finger domains are one of the most common structural motifs in eukaryotic cells, which employ the motif in some of their most important proteins including. The ccch zinc finger motif has been found in proteins from organisms ranging from man to yeast 918. Structural classification of zinc fingers nucleic acids. Zinc fingers small and mighty our cells, on the other hand, often use a zinc atom to take a short cut.
This motif is found in several eukaryotic checkpoint and dna repair proteins, such as chfr and aplf. Recently, glis1 was identified as a reprogramming factor and can replace the cmyc oncogene maekawa et al. In addition, new structural studies of proteins containing the classical cys 2his 2 zinc finger motif have led to. Based on the number, localization, and arrangement of zfs within a molecule, c2h2type znfs can be divided into 4 classes. The crystal structure of a two zincfinger peptide reveals.
Zinc finger transcription factors or zftfs, are transcription factors composed of a zinc finger binding domain and any of a variety of transcriptionfactor effectordomains that exert their modulatory effect in the vicinity of any sequence to which the protein domain binds. Pdf cys2his2 c2h2type zinc fingers are widespread dna binding motifs in eukaryotic. The first structure of a zinc finger dna complex revealed a fairly simple mechanism for dna recognition 4. Although multiple dof proteins associated with diverse gene promoters have recently been identified in a variety of plants, their physiological functions and regulation remain elusive. However, little is known about their potential negative roles in root hair initiation and elongation. Given the wide variety of zincfinger domains, znfs are able to interact. Herein we describe the generation and characterization of a family of zinc finger domains developed for the recognition of each of the 16 possible 3bp dna binding sites having the sequence 5. Originally coined to describe the finger like appearance of a hypothesized structure from xenopus laevis transcription factor iiia, the zinc finger. The c2h2 zinc finger motif, which comprises 20 to 30 amino acids containing two cys and two his residues coordinated by a zinc atom, has proven to be particularly versatile for protein engineering applications.
A zinc finger is stabilized by zinc interactions and hydrophobic interactions. Some forms of zinc finger have four cysteine residues bound to the zinc ion. Engineering efforts led to the discovery of a set of general rules that enable obtaining zinc. Oct 05, 2012 zinc finger protein motif that forms a compact globular structure that coordinates one or more zn ions. A zinc finger motif containing protein is essential for chloroplast rna editing. The discovery of zinc fingers and their applications in. The cys2his2type zinc finger, also called the classical or tfiiiatype finger, is one of the bestcharacterized dnabinding motifs found in eukaryotic transcription factors. An account is given of the discovery of the classical cyshis zinc finger, arising from the interpretation of biochemical studies on the interaction of the protein transcription factor iiia with 5s rna, and of structural studies on its structure and its interaction with dna. Zinc finger proteins of the classical cys2his2 type are the most frequently used class of transcription factor and account for about 3% of genes in the human genome1,2. Given the wide variety of zinc finger domains, znfs are able to interact.
Zinc finger protein an overview sciencedirect topics. The crystal structure of a two zinc finger peptide reveals an extension to the rules for zinc finger dna recognition. Zinc finger motif an overview sciencedirect topics. The finger is a selfcontained domain stabilized by a zinc.
This modular approach is so appealing that researchers are currently trying to design artificial zinc fingers with different specificities. Meiotic caryokinesis nuclear division has been extensively studied in many organisms, while mechanisms underlying meiotic cytokinesis remain elusive. Some 700 or more of our 30,00040,000 genes encode zinc finger. Snitrosation on zinc finger motif of parp1 as a mechanism of dna repair inhibition by arsenite article pdf available in oncotarget 749 october 2016 with 83 reads how we measure reads. Engineering polydactyl zincfinger transcription factors. Arabidopsis zinc finger protein1 acts downstream of gl2 to. These zfps can be fused with effector domains that confer. Zinc finger nucleases as tools to understand and treat human. Chemically synthesized zinc finger molecules as nano. The qtype zinc fingers contain a conserved motif, qalggh, and are plant specific, whereas c type zinc fingers are found in other organisms as well. A single zinc finger motif in the silencing factor rest.576 452 254 1238 564 1222 800 1571 470 976 621 1267 1547 428 1546 539 618 156 497 387 1490 241 1100 492 711 262 497 349 972 484 435 1296 1200 1481 290 243 786 1058 249 174 621 281 860 1339 1141 1281 546