Dnabinding motif is the cysteinehistidine cys2his2 zinc finger in the human genome and most of the multicellular animals. Identification of a substrate recognition domain in the. Specific interaction of zinc finger protein com with rna. Zinccontaining dnabinding motif article about zinc. For a given c2h2 zinc finger protein, we predict a position weight matrix representing its dna binding specificity and display it as a sequence logo. Ripening, including softening, is a critical factor in determining the postharvest shelflife of fruit and is controlled by enzymes involved in cell wall metabolism, starch degradation, and hormone metabolism. Zinc finger tools provides tools for selecting zinc finger protein zfp target sites and for designing the proteins that will target them.
This result can be used further to search genomic sequences for putative binding sites. The finger itself comprises 23 amino acids, and the linker between fingers is usually 7 v8 amino acids. Previous work showed that the drugs bind to the e3 ubiquitin ligase cereblon, which then targets for degradation two specific zinc finger zf transcription factors with a role in cancer development. Changing the amino acids at certain key positions generates zinc finger zf motifs with different triplet sequences and varying binding specificities 1, 2. Several members of the snf2 family of dnadependent atpases including smarcal1 swisnfrelated matrixassociated actindependent regulator of chromatin subfamily alike protein 1, 3 hltf helicaselike transcription factor and zranb3 zinc finger ran binding domain containing 3 are replication stress response proteins that catalyze fork. Artificial transcription factors atfs are composed of dnabinding and functional domains. The atzp1 gene contains a 615bp coding sequence including the stop codon encoding a 22kd protein with 204 amino acids. Exploiting the recognition code for elucidating the mechanism. Zinc finger motif article about zinc finger motif by the.
This proportion depends on the specific organism or tissue under consideration, which affects also the relative usage of the various metals. Most existing tools for predicting dna binding specificity in zinc fingers are trained on data obtained from naturally occurring proteins, thereby skewing the predictions. The aminoterminal portion has a chcc motif that coordinates zinc in a manner similar to the canonical cchh and cchc zinc finger motifs. C2h2 zinc finger proteins greatly expand the human regulatory. Here, we used a transcriptomicsbased approach to identify transcriptional regulatory components associated with texture, ethylene, and starch degradation in ripening kiwifruit. C dna sequences of the binding sites of blimp1 among the seven species, and the sequences logo generated by these dnabinding sequences. Motifs in dna and rnabinding proteins whose amino acids are folded into a single structural unit around a zinc atom. Atzp1 is a typical c2h2type zinc finger protein containing an ear motif. The encoded protein suppresses expression of the alphafetoprotein gene by binding to an atrich enhancer motif. Molecular mechanism of rna recognition by zincfinger. Zinc finger transcription factors or zftfs, are transcription factors composed of a zinc fingerbinding 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 zinc finger protein transcription factors can be encoded by genes small enough to fit a number of such genes into a. Researchers have utilized different design strategies to create novel zinc finger peptides by reengineering the c2h2type zinc finger motif, the his4type zinc finger protein and the at. We demonstrate that the seedpreferred gene gmzf351, encoding a tandem ccch zinc finger protein, is selected during domestication. Interaction and cooperation of mi transcription factor.
Zap selectively binds to cgdinucleotideenriched rna sequences and recruits multiple rna degradation machines to degrade target viral rna. Protein motifs dna binding, leucine zipper, membrane spanning, zinc finger. Prediction of dnabinding specificity in zinc finger proteins. Zf domains function as modular units that primarily recognize dna sites of 3 bp. For a given c 2 h 2 zinc finger protein, we predict a position weight matrix representing its dna binding specificity and display it as a sequence logo. Nucleicacid binding motif in transcriptional elongation factor tfiis and rna polymerases. Find out information about zinccontaining dnabinding motif. Design of a zinc finger protein binding a sequence upstream. Nonbasecontacting residues enable kaleidoscopic evolution. Here, we show that the c2h2type zinc finger protein named zinc finger protein1 atzp1, which contains an erfassociated amphiphilic repression ear motif. B wnt1 gene structure and dnabinding site position of blimp1 among seven species. Themimi mutant mice show microphthalmia, depletion of pigmentation in both hair and eyes.
Dec 22, 2016 engineering zinc finger protein motifs for specific binding to doublestranded dna is critical for targeted genome editing. This form lets you paste a protein sequence, select the collections of motifs to scan for, and launch the search. C2h2 zinc finger proteins greatly expand the human. This flexibility has made it an especially good scaffold for design of dna binding proteins with new specificities.
A zinc finger motifcontaining protein is essential for. Zinc finger znf domains are relatively small protein motifs which contain multiple finger like protrusions that make tandem contacts with their target molecule. In humans, replication protein a is the bestunderstood member of this family and is used in processes where the double helix is separated, including dna replication, recombination and dna repair. 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. The cys2his2 zinc finger motif is the ideal structural scaffold on which to construct a sequencespecific. Zinc finger dna binding proteins typically contain two or more zinc fingers. Cutoff score click each database to get help for cutoff score pfam evalue ncbicdd. However, the binding sites and functions of the majority of c2h2zf proteins remain unknown. Moreover, these mostly neglect the cooperativity exhibited by zinc fingers.
Some dnabinding domains may also include nucleic acids in their folded structure. Thalidomide and its analogs improve the survival of patients with multiple myeloma and other blood cancers. Zincfinger protein cnbp alters the 3d structure of lncrna. The motif takes its name from the loop of amino acids that protrudes from the zincbinding site and is described as the cys 2 his 2 finger. Structures of dnabinding mutant zinc finger domains. You are using the latest 8th release 2020 of jaspar. Three methyl thiolates were formed from the cysteinate coordinates. A web tool for predicting dnabinding specificity in. An algorithm for identifying zinc finger binding motifs in. Exploiting the recognition code for elucidating the mechanism of. A dnabinding domain dbd is an independently folded protein domain that contains at least one structural motif that recognizes double or singlestranded dna. May 21, 2019 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. Interestingly, cnbp a zinc finger transcription factor antagonizes this function by binding to the agil motif of bvht 3.
Cys2his2 zinc finger c2h2zf proteins represent the largest class of. Additionally, metal ions play a decisive role in stabilizing the structure of nucleic acids. The leucine zipper is a dimerisation domain occurring mostly in regulatory and thus in many oncogenic proteins. Dna conformation induces adaptable binding by tandem zinc. The zinc is held in a tetrahedral structure formed by the conserved cys and his residues. Zinc finger specificity prediction is based upon random forest model enter query sequence. Accordingly, we were curious to know if binding with cnbp affects bvht. Enter a dna sequence to be scanned for target sites 10 kb max. Cys2his2like fold group c2h2type zinc finger proteins promote root hair growth and development by regulating their target genes. Motif scanning means finding all known motifs that occur in a sequence. Most existing tools for predicting dnabinding specificity in zinc fingers are trained on data obtained from naturally occurring proteins, thereby skewing the predictions. Automatically discovered structural features are able to capture some characteristic spatial configurations of amino acids in proteins. A document deals with the interpretation of the match scores.
To construct a valid atf, it is necessary to design suitable dnabinding and functional domains. In cardioviruses, l is a small 8 kda, highly acidic protein with two putative structural domains. A zinc finger motif is a dnabinding domain genes vii. Helixturnhelix, zinc finger, motifs are combinations of secondary structures in proteins with a specific structure and a specific function. Prediction of dnabinding proteins from relational features. These zfps can be fused with effector domains that confer transcriptional activation or repression activity. Zinc finger motif was first found in the xenopus transcription factor iiia, and zinc finger protein is now regarded as one of the most abundant protein family in eukaryotic genomes. Engineering zinc finger protein motifs for specific binding to. Zinc finger, c4h2type ipr018482 prediction tool for zincfinger proteins, which, given a nucleotide sequence, finds the possible binding sites of zincfingers and returns the amino acid sequences of their recognition helices in this case, amino acids at position. Helixturnhelix, zinc finger, homeobox domain, hairpinbeta motif, calcium binding motif, betaalphabeta motif, coiledcoil motifs. The alpha helices in each finger interact with 3 base pairs of dna, typically interacting with contiguous 3 base pair recognition sites. Binding to a longer dna sequence improves the specificity of the zf attaching to its target site and only a dna sequence having six triplets or more is unique in the human genome.
Mar 19, 2008 artificial transcription factors atfs are composed of dna binding and functional domains. This site includes information about the zinc finger consortium, including. Engineering zinc finger protein motifs for specific dna targets in genomes is critical in the field of genome engineering. Seed oil is a momentous agronomical trait of soybean glycine max targeted by domestication in breeding. However, little is known about their potential negative roles in root hair initiation and elongation.
A small structural domain that is organized around a zinc ion and is found in many generegulatory proteins explanation of zinccontaining dnabinding motif. Michael sf, kilfoil vj, schmidt mh, amann bt, berg jm. Within each finger, we use the first zinccoordinating his in each finger as a reference position 0, residues preceding this, at positions. The bacteriophage mu com is a small zinc finger protein that binds to its cognate mom mrna and activates its translation. Dataset transfac predicted transcription factor targets. Zinc finger is a small protein structural motif important for binding dna, rna, proteins and lipids. Although multiple oilrelated genes have been uncovered, knowledge of the regulatory mechanism of seed oil biosynthesis is currently limited. In the classic zinc finger, one zinc atom is bound to two cysteines and two. Zinc fingers are structurally diverse and exhibit a wide range of functions, from dna or rna binding to proteinprotein interactions and membrane association. A distinct group of dna binding proteins are the dna binding proteins that specifically bind singlestranded dna. The deposited coordinates for the hiv1 nucleocapsid protein were used to construct a representative structural model of a cchc zinc finger.
Jaspar a database of transcription factor binding profiles. Further analysis showed that the mutant znfo possessing only the first zinc finger motif is cytoplasmic while the mutant with the last 7 zinc fingers removed is located in the nucleus. This suggests that the real nls is located in the second zinc finger motif of znfo, although the exact nls sequence has yet to be identified. The knowledge of their target dnabinding sequences is vital to develop chimeric proteins for targeted genome engineering and sitespecific gene correction.
The mi locus of mice encodes a member of the basichelixloophelix leucine zipper bhlhzip 1 protein family of transcription factors hereafter called mitf 1, 2. Zn, a chemical element of group ii of mendeleevs periodic system. There is a need to develop a computational resource of zinc finger proteins zfp to identify the. A bluish white metal, zinc occurs in the form of five stable isotopes, with mass numbers 64. The first protein to be identified with a dof domain was mnb 1azmdof1 of maize, which. Identification of a substrate recognition domain in the replication stress response protein zinc finger ranbinding domaincontaining protein 3.
The meme suite provides a large number of databases of known motifs that you can use with the motif enrichment and motif comparison tools. Some dna binding domains may also include nucleic acids in their folded structure. Role of a novel oocytespecific krabcontaining zinc finger. Threedimensional solution structure of a single zinc finger dnabinding domain. To construct a valid atf, it is necessary to design suitable dna binding and functional domains. Nmr structure of the mengovirus leader protein zincfinger. D the sequence of the 34 bp oligo representing the minimal binding site is aligned to the inferred prdm9 dom2 binding motif 6, 21 and the zincfinger array of prdm9 dom2 amino acids at positions 1, 3, and 6 relative to the. Jaspar is an openaccess database of curated, nonredundant transcription factor tf binding profiles stored as position frequency matrices pfms and tf flexible models tffms for tfs across multiple species in six taxonomic groups. This site serves as an interface between a users input and a set of prediction algorithms that are able to create the mentioned lo. The process of proteindna binding has an essential role in the biological processing of genetic information. As we demonstrate for the wellcharacterized na binding motif, c2h2 zinc finger, our method is completely independent of the protein fold and can successfully distinguish between dna binding zinc finger domains and those which bind rna even within the same protein, as in the transcription factor tfiiia 41. Apr 22, 2020 prosite is complemented by prorule, a collection of rules based on profiles and patterns, which increases the discriminatory power of profiles and patterns by providing additional information about functionally andor structurally critical amino acids more. A zinc finger is a small, functional, independently folded domain that. These domains can be fused together to create proteins that can bind a chosen dna sequence.
It has been estimated that 3040% of proteins require one or more metal ions to be able to carry out their biological function in cells. We use relational machine learning to predict dnabinding propensity of proteins from their structures. The zinc finger is a common structural motif in many protein dna binding domains. It explains the structure and role of zinc finger motif in proper functioning of dna and rna binding. Motifs in protein sequences school of computing and. The biochemical and evolutionary mechanisms that underlie the diversity of this dna binding domain exclusively in metazoans are, however, mostly unknown. Each finger binds to a threebase pair dna template in the major groove.
In this study, we demonstrate that ctbp2associated zinc finger proteins cooperate for the delicate control of exit from pluripotency by regulating the epigenetic states of h3k27 on active esc gene regions. Genomewide identification and expression profiling of the. Zinc finger proteins zfps contain a fingershaped fold that coordinates zinc ions with a combination of cysteine and histidine residues for their fold stabilization. We have taken a comprehensive approach to the generation of novel dna binding zinc finger domains of defined specificity. The only welldocumented and most significant domain found in this family is the ran binding protein 2 type zinc finger motif, which is a conserved 30aminoacid consensus x 2 gdwicx 2 cx 3 nfarrx 2 cxrcx 2prpex 2.
Zinc finger proteins orchestrate active gene silencing during. C dna sequences of the binding sites of blimp1 among the seven species, and the sequences logo generated by these dna binding sequences. Structurebased prediction of c2h2 zincfinger binding specificity. Conservation analysis of zinc finger motifs of bmblimp1. Zinc finger proteins zfps contain a finger shaped fold that coordinates zinc ions with a combination of cysteine and histidine residues for their fold stabilization. Click here to see descriptions of the available motif databases. 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.
A small tertiary protein structural motif of higher organisms, in which parts of a protein fold around a zinc molecule, acting as a hook to attach activator proteins to dna. A dbd can recognize a specific dna sequence a recognition sequence or have a general affinity to dna. Engineering zinc finger protein motifs for specific binding to doublestranded dna is critical for targeted genome editing. One of the ctbp2 binding zinc finger proteins, zfp217 figure 1 is known as an oncogenic protein associated in various cancers 16,17,61.
Zinc fingers are structurally diverse and exhibit a wide range of functions, from dna or rnabinding to proteinprotein interactions and membrane association. To predict target genes for zinc finger protein binding, the top 5% of sequences from the predicted results were fed into match from the transfac package. Zinc finger tools provides tools for selecting zinc finger protein zfp target sites and for. The mitf encoded by the mutant mi allele mimitf deletes one of four consecutive arginines in the basic domain 1, 3, 4. Arabidopsis zinc finger protein1 acts downstream of gl2 to.
Gnn3 phage display libraries of zinc finger proteins were created and. The strong matches of the binding site to the motif are in red. Design of a zinc finger protein binding a sequence. Prosite is complemented by prorule, a collection of rules based on profiles and patterns, which increases the discriminatory power of profiles and patterns by providing additional information about functionally andor structurally critical amino acids more. Interestingly, cnbp a zincfinger transcription factor antagonizes this function by binding to the agil motif of bvht 3.
Symbol zn a bluishwhite, lustrous metallic element that is brittle at room temperature but malleable with heating. The motif is composed of a zinc knuckle followed by a loop, a. In silico prediction of dna binding with one finger dof. Zinc finger motif definition of zinc finger motif by the. Zinc finger dna binding domain definition of zinc finger. The zinc finger motif array is highly divergent, indicating that most proteins will have distinctive binding sites and perform different functions. Zinc finger motif was named based on the zinc binding amino acids and the requisition of zinc ions to stabilize its structure. Comprehensive analysis of the binding specificities of c2h2 zinc finger proteins reveals their dna recognition code. Specific interaction of zinc finger protein com with rna and. 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. Zincfinger protein cnbp alters the 3d structure of.
Here, we show that the c2h2zf expansion in metazoans is facilitated by contribution of nonbase. Zinc finger antiviral protein zap is a host antiviral factor that specifically restricts a wide range of viruses. Prediction of dnabinding proteins from structural features. 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 between amino acids 59 and 64. The c2h2 zinc finger c2h2zf is the most numerous protein domain in many metazoans, but is not as frequent or diverse in other eukaryotes. Defining the human c2h2 zinc finger degrome targeted by. The mom protein, in turn, elicits a chemical modification momification of the bacteriophage genome, rendering the dna resistant to cleavage by bacterial restriction endonucleases, and thereby protecting it from defense mechanisms of the host. The cys2his2 zinc finger motif is the ideal structural scaffold on which to construct a sequencespecific protein. Treble clef fingera functionally diverse zincbinding. Exploiting the recognition code for elucidating the.
A web tool for predicting dnabinding specificity in c2h2 zinc. In order to enhance its utility and to validate the prediction results, bindpredict tool is interconnected with bindpredict db. From these results, we were able to construct a zifibi zinc finger binding site database. B wnt1 gene structure and dna binding site position of blimp1 among seven species. Information on the occurrence of zinc finger protein motifs in genomes is crucial to the developing field of molecular genome engineering. A amino acids of zinc finger motif analysis among 21 species. Motifs in dna and rna binding proteins whose amino acids are folded into a single structural unit around a zinc atom. The carboxylportion of l is highly enriched in acidic residues and has several potential tyr or thr. Here, a zincbinding structural motif that we term the treble clef finger is described. Transcriptome analysis identifies a zinc finger protein. A dna binding domain dbd is an independently folded protein domain that contains at least one structural motif that recognizes double or singlestranded dna.
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