Initially used to define a repeated zincbinding motif with dna binding. Zinc finger motif an overview sciencedirect topics. This is an evolutionarily conserved proteinprotein interaction domain that is found at the n terminus of c 2h 2type zinc. Zinc fingers are structurally diverse and exhibit a wide range of functions, from dna or rnabinding to proteinprotein interactions and membrane association. Structural analyses of zinc finger domains for specific interactions. We have developed a novel and simple method to rationally design artificial zinc finger proteins azps targeting diverse dna sequences using a nondegenerate recognition code table. Structure based design of protein linkers for zinc finger. A novel dnabinding domain that may form a single zinc. Introduction in 2009, wolf and goff 1 revealed that zinc finger protein 809 zfp809 has a central role in the transcriptional suppression of moloney murine leukemia virus momlv.
Arsenite binds to the zinc finger motif of tip60 histone. Zinc finger proteins are the largest transcription factor family in human genome. Zinc finger specificity prediction is based upon random forest model enter query sequence. In addition, new structural studies of proteins containing the classical cys 2his 2 zinc finger motif have led to.
The limdouble zinc finger motif functions as a protein dimerization domain. C2h2 cyscyshishis motif zinc finger proteins are members of a large superfamily of nucleicacidbinding proteins in eukaryotes. 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. Except for the zinc finger motif, no other annotated domain or motif was found in the oz1 family. Zinc finger proteins in cancer progression journal of. The crystal structure ofa complex containing the three zinc fingers from zif268 a mouse immediate early protein andaconsensus dna. An apoptosisinhibiting baculovirus gene with a zinc. A zinc finger motif is a dnabinding domain genes vii. For in vivo analysis of the tnpa zinc finger domain, the minitn4555 construct, pfd660. We have included the structure of a zinc finger from the a subunit of rna polymerase ii 1i3q. Western blot images showing the effect of mutations in critical cysteine residues of the c3htype zinc finger of tip60, i. This motif is found in several eukaryotic checkpoint and dna repair proteins, such as chfr and aplf.
The finger itself comprises 23 amino acids, and the linker between fingers is usually 7 v8 amino acids. Together, the zinc transcription factor motif and the transcription factor activates or. Pdf isolation of a zinc finger gene consistently deleted. Pabo the zinc finger dnabinding motif occurs in many proteins that regulate eukaryotic gene expression. The first and the second zinc finger without the additional base pairs dock to the dna with zfm1 folding close to the native state and fulfilling all the intramolecular contacts, however the zinc fingers zfm2 and zfm3 fail to fold close to the native state pdb 1aay, most likely because the linker length is insufficient to skip the 3. Structural classification of zinc fingers nucleic acids. 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 motif takes its name from the loop of amino acids that protrudes from the zinc binding site and is described as the cys 2 his 2 finger. 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. Classical zinc finger domains and metal coordination.
In arabidopsis, over 600 genomicallyencoded cs are modified to us in organelle transcripts, altering the encoded amino acids and creating stop and start codons. There is a need to develop a computational resource of zinc finger. Zincfinger proteins in health and disease cell death. Author summary transcripts encoding chloroplast and mitochondrial proteins of flowering plants are profoundly affected by rna editing.
This is a pdf file of an unedited manuscript that has been accepted for publication. A zinc finger is a small, functional, independently folded domain that coordinates one or more zinc ions to stabilize its structure through cysteine andor histidine residues. A zinc finger motifcontaining protein is essential for. Tobacco zft1, a transcriptional repressor with a cys2his2 type zinc finger motif that functions in sperminesignaling pathway article pdf. Arsenite does not induce dosedependent decrease in protein level of any three zinc finger mutants of tip60, i. R feuerstein, x wang, d song, n e cooke, and s a liebhaber department of genetics, university of pennsylvania school of medicine, philadelphia 191046145. If you do not see its contents the file may be temporarily unavailable at the journal website or you do not have a pdf plugin installed and enabled in your browser. Zinc finger homeodomain proteins zhd constitute a plantspecific transcription factor family with a conserved dna binding homeodomain and a zinc finger motif. In addition, new structural studies of proteins containing the classical cys2his2 zinc finger motif have led to novel insights into mechanisms of dna binding and. A zing finger is a transcription factor motif, also known as a protein that helps the main transcription factor in regulating gene expression. We believe that this method is a powerful technique for the isolation and characterization of zincfinger encoding genes. How might the arginine side chain positivelycharged shown on your model be involved in dna binding. Pdf tobacco zft1, a transcriptional repressor with a. One such motif is the zinc finger in which a specific domain of the protein is arranged into a finger like structure where two beta sheets and one.
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. Information on the occurrence of zinc finger protein motifs in genomes is crucial to the developing field of molecular genome engineering. How is a zinc atom involved in the stabilization of the zinc finger motif. Genomewide characterization of zhd genes has been carried out in several model plants. The zinc finger binds a zinc ion in order to stabilize its threedimensional structure consisting of a twostranded antiparallel. Structures have recently been reported for many new zinc finger domains with novel topologies, providing important insights into structurefunction relationships. Folding a toober model of the zinc finger questions 2. Medaka zmynd10 encodes a myndtype zinc finger motif near its c terminus. 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. Molecular cloning of two dnabinding proteins of maize that are structurally different but interact with the same sequence motif.
Given the wide variety of zincfinger domains, znfs are able to interact. As a service to our customers we are providing this early version of the manuscript. Zinc finger nucelases genome editing nucleases ii zfn vs talens duration. Loss of zinc finger myndtype containing 10 zmynd10.
Zinc finger protein an overview sciencedirect topics. Phosphorylation of the leukemic oncoprotein evi1 on serine. The zinc finger dnabinding motif occurs in many proteins that regulate eukaryotic gene expression. A novel polyadpribosebinding zinc finger pbz motif is identified. Full text get a printable copy pdf file of the complete article 1. 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. Hyonemyong eun, in enzymology primer for recombinant dna technology, 1996 ii zinc finger motif. Functional and structural features of zinc finger protein 809. Describe the secondary structural elements that comprise a zinc finger. Zinc finger gatalike protein 1 zglp1 zinc finger gatalike protein 1 zglp1, also known as glp1 is a nuclear protein containing two zinc fingers, one of which is highly homologous to the conserved gata zinc finger dnabinding motif. The zinc is held in a tetrahedral structure formed by the conserved cys and his residues.
The table was constructed based on known and potential dna base. Pentatricopeptide proteins are known to bind to ciselements near c targets of. If zero default, each motif will include the entire length of one zinc finger array a zinc finger array is a set of zinc fingers that are separated by linkers of 46 amino acids maximum base selectivity the folddifference between the likelihoods of the most and least preferred bases at the position with maximum base selectivity. Zinc fingers are short protein motifs composed of two or three. The diverse combinations and functions of zinc finger motifs make zinc finger proteins versatile in biological processes, including development, differentiation, metabolism and autophagy. The predicted sequence of the iap polypeptide exhibited no significant homology to p35 but contained a zinc finger like motif which is also found in other genes with the potential to regulate apoptosis, including several mammalian protooncogenes and two insect genes involved in embryonic development. Polyadpribosebinding zinc finger motifs in dna repair. Over the last few decades, increasing evidence reveals the potential roles of zinc finger proteins in. Two cysteine and two histidine residues located in certain positions bind. The limdouble zincfinger motif functions as a protein. The zinc finger motif is commonly found in eukaryotic transcription factors, which are proteins that bind to specific. The knowledge of their target dnabinding sequences is vital to develop chimeric proteins for targeted genome engineering and sitespecific gene correction. Each c2h2 zinc finger motif has a typical consensus sequence of. Four lxxll motifs that are predicted in human are shown above the alignment, and the one that is conserved in medaka is boxed.
In order to disrupt the zinc finger motif, the tnpamaltose binding protein fusion. The c1 domain contains a zinc finger motif that forms the binding site for diacylglycerol and phorbol esters in the context of phospholipids. The table permits identification of an amino acid for each position. Specifically, the zinc in the zinc finger helps stabilize and coordinate the transcription factor protein onto the desired dna or rna sequence. Isolation of a zinc finger gene consistently deleted in digeorge syndrome. 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. The stimulusmediated generation of diacylglycerol effectively plugs a hydrophilic site in the c1 domain, making the surface more hydrophobic, so allowing c1 to become buried in the membrane zhang et al.
Gal4 constitutes, a completely new structural type of zinc finger 2. The zinc finger is a common structural motif in many protein dna binding domains. The discovery of zinc fingers and their applications in. Zfps are divided into many families on the basis of the conserved zinc finger motif andor other notable. Rational design of artificial zincfinger proteins using a.
Zinc finger structures are as diverse as their functions. Zinc finger protein motif that forms a compact globular structure that coordinates one or more zn ions. 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. Members of the zhd protein family play important roles in plant growth, development, and stress responses.
Pangas, aleksandar rajkovic, in knobil and neills physiology of reproduction fourth edition, 2015. The finger is a selfcontained domain stabilized by a zinc ion ligated to a pair of cysteines and a pair of histidines. Pdf zincfinger proteins in health and disease researchgate. Serine 196 is on the surface of the zinc finger domain, which allows it to accommodate the phosphate group figure 2a and b. 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.
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