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At least 91 records · Page 5Linked to original sources
PubMed2006

Finger synergies during multi-finger cyclic production of moment of force.

We investigated multi-finger synergies stabilizing the total moment of force and the total force when the subjects produced a quick cyclic change in the total moment of force. The seated subjects performed the task with the fingers of the dominant arm while paced by the metronome at 1.33 Hz. They were required to produce a rhythmic, sine-like change in the total pronation-supination moment of force computed with respect to the midpoint between the middle and ring fingers. The framework of the uncontrolled manifold hypothesis was used to compute indices of stabilization of the total moment and of the total force across 20 cycles. Variance of the total moment showed a cyclic pattern with peaks close to the peak rate of the moment change. Variance of the total force was maximal close to peak moment into supination. Higher magnitudes of the moment directed against the required moment direction (antagonist moment) were produced by individual fingers during supination efforts as compared to pronation efforts. Indices of multi-finger synergies showed across-trials stabilization of the total moment over the whole cycle but not of the total force. These indices were smaller during supination efforts. We conclude that the central nervous system facilitates multi-finger synergies stabilizing the total rotational action across a variety of tasks. Synergies stabilizing the total force are not seen in tasks that do not explicitly require accurate force control. Pronation efforts are performed more efficiently and with better stabilization of the action.

Adult↗
PubMed2004

Finger skin cooling on contact with cold materials: an investigation of male and female responses during short-term exposures with a view on hand and finger size.

This study investigated the independent effects of hand anthropometry and gender upon contact cooling responses. Subjects were selected for matching hand/finger size between genders, with equal variation between individuals of each group. Fourteen volunteers (7 male, 7 female) participated, touching blocks of aluminium and stainless steel using the first phalanx of the index finger with a contact force of 1.0 N and 9.8 N, at surface temperatures of -2 degrees C and -10 degrees C. Conditions were selected in order to elicit varying rates of skin cooling upon contact. Contact temperature ( T(C)) of the finger-pad was measured over time using a T-type thermocouple. Overall, no significant difference was found between the cooling responses of males and females. In order to investigate whether differences in hand anthropometry correlated with contact cooling response, a multiple regression approach was used. Analyses of the residual variance in contact cooling data, after the effects of material type, surface temperature and finger contact force had been accounted for, showed that, under slow cooling conditions (>45 s to reach T(C)=1 degrees C), hand size correlated significantly with contact cooling response only when represented by index finger volume ( P<0.05), but gender did not. Whilst under fast cooling conditions (<25 s to reach T(C)=1 degrees C), hand size did not correlate significantly with contact cooling response at all, but gender had a significant effect ( P<0.001). Under slow cooling conditions, a larger finger (and in most cases hands) provides a higher heat content, thus giving a slower skin cooling speed. Under fast cooling conditions, the significantly longer time required for males to reach a T(C) of 1 degrees C, despite matching hand and finger size, is attributed to higher epidermal insulation provided by the thicker stratum corneum, combined with the higher starting skin temperature observed in the "slightly cool" environment.

Adaptation, Physiological↗
PubMed2005

Reactivity of zinc finger cysteines: chemical modifications within labile zinc fingers in estrogen receptor.

Estrogen receptor (ER, alpha isoform) is a 67 kDa zinc finger transcription factor that plays a fundamental role in both normal reproductive gland development and breast carcinogenesis, and also represents a critical molecular target for breast cancer therapy. We are investigating the structural consequences of chemical exposures thought to modify essential zinc finger cysteine residues in human ER. The current study employs mass spectrometry to probe ER zinc finger structural changes induced by a redox-reactive vitamin K3 analog, menadione; a commonly used cysteine alkylator, iodoacetic acid; and a thiol alkylating fluorophore, monobromobimane. Although they are slower to react, the sterically bulkier reagents, monobromobimane and menadione, effectively alkylate the most susceptible ER zinc finger cysteine sulfhydryl groups. Menadione arylation results first in Michael addition of the hydroquinone followed by rapid oxidation to the corresponding quinone, evidenced by a 2 Da mass loss per cysteine residue. Mass spectrometric analysis performed under MALDI conditions reveals both hydroquinone and quinone forms of arylated menadione, whereas only the quinone product is detectable under ESI conditions. Tandem mass spectrometry of a synthetic peptide encompassing the C-terminal half of the structurally more labile second zinc finger of ER (ZnF2B) demonstrates that the two nucleophilic thiols in ZnF2B (Cys-237, Cys-240) are not chemically equivalent in their reactivity to bromobimane or menadione, consistent with their unequal positioning near basic amino acids that affect thiol pKa, thereby rendering Cys-240 more reactive than Cys-237. These findings demonstrate important differential susceptibility of ER zinc finger cysteine residues to thiol reactions.

Binding Sites↗
PubMed1991

Alternating zinc fingers in the human male associated protein ZFY: 2D NMR structure of an even finger and implications for "jumping-linker" DNA recognition.

ZFY, a sex-related Zn-finger protein encoded by the human Y chromosome, is distinguished from the general class of Zn-finger proteins by the presence of a two-finger repeat. Whereas odd-numbered domains and linkers fit a general consensus, even-numbered domains and linkers exhibit systematic differences. Because this alternation may have fundamental implications for the mechanism of protein-DNA recognition, we have undertaken biochemical and structural studies of fragments of ZFY. We describe here the solution structure of a representative nonconsensus (even-numbered) Zn finger based on 2D NMR studies of a 30-residue peptide. Structural modeling by distance geometry and simulated annealing (DG/SA) demonstrates that this peptide folds as a miniglobular domain containing a C-terminal beta--hairpin and N-terminal alpha-helix (beta beta alpha motif). These features are similar to (but not identical with) those previously described in consensus-type Zn fingers (derived from ADR1 and Xfin); the similarities suggest that even and odd ZFY domains bind DNA by a common mechanism. A model of the protein-DNA complex (designated the "jumping-linker" model) is presented and discussed in terms of the ZFY two-finger repeat. In this model every other linker is proposed to cross the minor groove by means of a putative finger/linker submotif HX4HX3-hydrophobic residue-X3. Analogous use of a hydrophobic residue in a linker that spans the minor groove has recently been described in crystallographic and 3D NMR studies of homeodomain-DNA complexes. The proposed model of ZFY is supported in part by the hydroxyl radical footprint of the TFIIIA-DNA complex [Churchill, M.E.A., Tullius, T.D., & Klug, A. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 5528-5532].

Amino Acid Sequence↗
PubMed1991

Alternating zinc fingers in the human male associated protein ZFY: refinement of the NMR structure of an even finger by selective deuterium labeling and implications for DNA recognition.

ZFY, a male-associated Zn-finger protein encoded by the human Y chromosome, exhibits a distinctive two-finger repeat: whereas odd-numbered domains fit a general consensus, even-numbered domains exhibit systematic differences. Do these odd and even sequences encode structurally distinct surfaces for DNA recognition? As a first step toward answering this question, we have recently described the sequential 1H NMR assignment of a representative nonconsensus Zn finger (designated ZFY-6T) based on 2D NMR studies of a 30-residue peptide [Kochoyan, M., Havel, T.F., Nguyen, D.T., Dahl, C.E., Keutmann, H. T., & Weiss, M.A. (1991) Biochemistry 30, 3371-3386]. Initial structural modeling by distance geometry/simulated annealing (DG/SA) demonstrated that this peptide retained the N-terminal beta-hairpin and C-terminal alpha-helix (beta beta alpha motif) observed in consensus Zn fingers. However, the precision of this initial structure was limited by resonance overlap, which led to ambiguities in the assignment of key NOEs in the hydrophobic core. In this paper these ambiguities are resolved by selective deuterium labeling, enabling a refined structure to be calculated by DG/SA and restrained molecular dynamics. These calculations provide a detailed view of the hydrophobic core and protein surface, which are analyzed in reference to previously characterized Zn fingers. Variant (even) and consensus (odd) aromatic residues Y10 and F12, shown in an "aromatic swap" analogue to provide equivalent contributions to the hydrophobic core [Weiss, M.A., & Keutmann, H.T. (1990) Biochemistry 29, 9808-9813], nevertheless exhibit striking differences in packing interactions: Y10--but not F12--contributes to a contiguous region of the protein surface defined by putative specificity-determining residues. Alternating surface architectures may have implications for the mechanism of DNA recognition by the ZFY two-finger repeat.

Amino Acid Sequence↗
PubMed2002

Interconversion between serine and aspartic acid in the alpha helix of the N-terminal zinc finger of Sp1: implication for general recognition code and for design of novel zinc finger peptide recognizing complementary strand.

In the typical base recognition mode of the C(2)H(2)-type zinc finger, the amino acid residues at alpha-helical positions -1, 3, and 6 make a contact with the base in one strand (the primary strand), and the residue at position 2 interacts with the base in a complementary strand (the secondary strand). The N-terminal zinc finger of the three-zinc-finger domain of Sp1 has inherently a unique five-base-pair binding mode in which the guanine bases are recognized in both strands. To clarify the effect of the amino acid at position 2 on DNA binding affinity and base specificity, we have created a library of the mutants by the interconversion between serine and aspartic acid in the N-terminal zinc finger of Sp1 and recombinant variants of finger order. Gel mobility shift and methylation interference assays showed that the combination of arginine and serine at positions -1 and 2, respectively, provides a newly strong guanine contact in the secondary strand and a higher binding affinity than that of wild-type Sp1. Of special interest are the facts that the mutant with lysine and aspartic acid at positions -1 and 2 in the alpha helix predominantly recognizes the bases in the secondary strand and that its DNA binding affinity is higher than that of the wild-type. The aspartic acid or serine at position 2 independently contributes to the DNA binding affinity and base specificity. The present results provide useful information for the design of a novel zinc finger protein with priority for the bases in the secondary strand.

Aspartic Acid↗
PubMed1997

Isolation and characterisation of a diverse family of Arabidopsis two and three-fingered C2H2 zinc finger protein genes and cDNAs.

In animal systems the C2H2 zinc finger protein (ZFP) gene family is the largest group of regulatory proteins and its members have a wide and important role in growth and development. It is likely that this family of ZFP transcription factors will also be important in plants. We have used a PCR approach employing highly degenerate oligonucleotide primers to isolate several Arabidopsis genomic and cDNA clones encoding potential ZFPs. In addition we have used the sequence information from these clones to identify two ESTs as members of this family. Five two-fingered and one three-fingered ZFPs have been identified. Outside of the zinc finger regions, there is considerable sequence diversity, including the sequence and length of the interfinger region; the expression pattern of each gene is different. This is the first report of the isolation of a three-fingered plant C2H2 ZFP gene and we discuss its possible evolutionary origin from two-fingered ZFP genes.

Amino Acid Sequence↗
PubMed1993

The crystal structure of a two zinc-finger peptide reveals an extension to the rules for zinc-finger/DNA recognition.

The Cys2-His2 zinc-finger is the most widely occurring DNA-binding motif. The first structure of a zinc-finger/DNA complex revealed a fairly simple mechanism for DNA recognition suggesting that the zinc-finger might represent a candidate template for designing proteins to recognize DNA. Residues at three key positions in an alpha-helical 'reading head' play a dominant role in base-recognition and have been targets for mutagenesis experiments aimed at deriving a recognition code. Here we report the structure of a two zinc-finger DNA-binding domain from the protein Tramtrack complexed with DNA. The amino-terminal zinc-finger and its interaction with DNA illustrate several novel features. These include the use of a serine residue, which is semi-conserved and located outside the three key positions, to make a base contact. Its role in base-recognition correlates with a large, local, protein-induced deformation of the DNA helix at a flexible A-T-A sequence and may give insight into previous mutagenesis experiments. It is apparent from this structure that zinc-finger/DNA recognition is more complex than was originally perceived.

Amino Acid Sequence↗
PubMed1994

Toward a code for the interactions of zinc fingers with DNA: selection of randomized fingers displayed on phage.

We have used two selection techniques to study sequence-specific DNA recognition by the zinc finger, a small, modular DNA-binding minidomain. We have chosen zinc fingers because they bind as independent modules and so can be linked together in a peptide designed to bind a predetermined DNA site. In this paper, we describe how a library of zinc fingers displayed on the surface of bacteriophage enables selection of fingers capable of binding to given DNA triplets. The amino acid sequences of selected fingers which bind the same triplet are compared to examine how sequence-specific DNA recognition occurs. Our results can be rationalized in terms of coded interactions between zinc fingers and DNA, involving base contacts from a few alpha-helical positions. In the paper following this one, we describe a complementary technique which confirms the identity of amino acids capable of DNA sequence discrimination from these positions.

Amino Acid Sequence↗
PubMed1996

A zinc finger gene from Onchocerca volvulus encodes a protein with a functional signal peptide and an unusual Ser-His finger motif.

The filarial parasite Onchocerca volvulus is the causative agent of river blindness. In order to identify genes potentially involved in parasite development we cloned a zinc finger-encoding gene from this species. The ovzf-1 gene represents one member of a family of related zinc finger genes. The predicted ovzf-1 translation product of 447 amino acids includes a hydrophobic signal peptide, which is followed by 13 contiguous finger motifs. The domains of fingers II-XIII display several conserved amino acids and a typical Krüppel-like Cys2-His2 motif. The first finger domain has the two conserved Cys residues replaced with Ser residues; however, it includes all additional amino acids typical of zinc finger domains. The N-terminal domain functions as a signal peptide, as it directs secretion of a reporter protein and a truncated Ovzf protein. Expression of an Ovzf protein via the secretory pathway was also confirmed by demonstrating attachment of N-linked carbohydrates to the recombinant protein. Although the recombinant Ovzf protein also includes a signal peptide, immunofluorescence analyses localize it inside a specific compartment of the infected insect cell. Expression of ovzf mRNA is developmentally regulated; no specific transcript is detected in adult female worms but in the infective L3. Identification of a secreted protein that might function in modulating gene expression of host cells provides an interesting tool for the study of parasite-host interaction on a biochemical and molecular level.

Amino Acid Sequence↗
PubMed2000

Interactions of CCCH zinc finger proteins with mRNA. Binding of tristetraprolin-related zinc finger proteins to Au-rich elements and destabilization of mRNA.

Macrophages derived from tristetraprolin (TTP)-deficient mice exhibited increased tumor necrosis factor alpha (TNFalpha) release as a consequence of increased stability of TNFalpha mRNA. TTP was then shown to destabilize TNFalpha mRNA after binding directly to the AU-rich region (ARE) of the 3'-untranslated region of the TNFalpha mRNA. In mammals and in Xenopus, TTP is the prototype of a small family of three known zinc finger proteins containing two CCCH zinc fingers spaced 18 amino acids apart; a fourth more distantly related family member has been identified in Xenopus and fish. We show here that representatives of all four family members were able to bind to the TNFalpha ARE in a cell-free system and, in most cases, promote the breakdown of TNFalpha mRNA in intact cells. Because the primary sequences of these CCCH proteins are most closely related in their tandem zinc finger domains, we tested whether various fragments of TTP that contained both zinc fingers resembled the intact protein in these assays. We found that amino- and carboxyl-terminal truncated forms of TTP, as well as a 77 amino acid fragment that contained both zinc fingers, could bind to the TNFalpha ARE in cell-free cross-linking and gel shift assays. In addition, these truncated forms of TTP could also stimulate the apparent deadenylation and/or breakdown of TNFalpha mRNA in intact cells. Alignments of the tandem zinc finger domains from all four groups of homologous proteins have identified invariant residues as well as group-specific signature amino acids that presumably contribute to ARE binding and protein-specific activities, respectively.

3' Untranslated Regions↗
PubMed1995

The cellular RING finger protein PML is not a functional counterpart of the herpes simplex virus type 1 RING finger protein Vmw110.

Herpes simplex virus type 1 (HSV-1) immediate early protein Vmw110 (also known as ICP0) is required for the fully efficient expression of viral genes during onset of lytic growth and for normal reactivation from latency. Both Vmw110 and the cellular protein PML are members of the RING finger family of zinc binding domain proteins, a family which includes an increasing number of examples from a wide evolutionary range. The function of the RING finger domain is unknown, and the question arises whether the RING finger (like several other examples of conserved domains) fulfils similar functions in these diverse proteins. Another link between Vmw110 and PML is that at early times of HSV-1 infection Vmw110 migrates to distinct nuclear structures which contain the PML protein. In order to test the possibility that PML and Vmw110, or their RING finger domains, fulfill similar functions, we have constructed recombinant viruses that express either intact PML, or a chimeric Vmw110 protein which contains the PML RING finger in place of its own. The results indicate that the PML and Vmw110 RING fingers are not functionally interchangeable, and that PML is not a cellular functional counterpart of Vmw110.

Animals↗
PubMed1992

Novel member of the zinc finger superfamily: A C2-HC finger that recognizes a glia-specific gene.

A novel member of the zinc finger superfamily was cloned by virtue of its binding to cis-regulatory elements of a glia-specific gene, the myelin proteolipid protein (PLP) gene. Named MyTI (myelin transcription factor I), this gene is most highly transcribed in the developing nervous system, where expression precedes induction of its presumptive target, PLP. Low levels of MyTI transcripts can be detected in nonneural tissues only by polymerase chain reaction analysis. Zinc is a necessary cofactor for DNA binding of MyTI, as the zinc-chelating agent 1,10-orthophenanthroline eliminates binding activity. Zinc may stabilize the DNA-binding domain of MyTI by coordinating three cysteine and one histidine residue in a Cys-X5-Cys-X12-His-X4-Cys (C2-HC) arrangement. The MyTI protein has six fingers of the C2-HC class arranged in two widely separated clusters. These two domains of DNA binding can function independently and recognize the same DNA sequence, suggesting that MyTI may contribute to the higher-order structure of a target promoter by simultaneously binding both proximal and distal sites. The six fingers are highly conserved, suggesting that they arose from successive duplication events, while the linker regions diverge in size and sequence. Both amino acid sequence comparisons and secondary-structure predictions indicate that the C2-HC fingers of MyTI do not resemble the zinc-mediated loops of C2-H2 fingers, C2-C2 fingers, or Cx clusters. MyTI may therefore be the prototype of a new structural family of zinc-stabilized DNA binding proteins.

Amino Acid Sequence↗
PubMed1997

Cloning, expression and mapping of a novel RING-finger gene (RNF5), a human homologue of a putative zinc-finger gene from Caenorhabditis elegans.

The RING-finger is a unique zinc-chelating domain involved in mediating protein-protein interactions. The extensive sequence homology within the RING-finger domain allowed us to clone a novel member of the RING-finger family of genes. This cDNA clone, designated RNF5 (Ring-finger protein 5), contained an open reading frame of 540 nucleotides. Its predicted amino acid sequence revealed significant homology to a hypothetical protein encoded by Caenorhabditis elegans cosmid C16C10.7. The expression of RNF5 was detected in a variety of human tissues. The RNF5 gene was mapped by fluorescence in situ hybridization to chromosome 6p21.31. Radiation hybrid mapping further assigned RNF5 to a region proximal to the major histocompatibility complex (MHC) on chromosome 6. RNF5 is the third RING-finger gene identified in the region proximal to MHC raising the possibility that the RING-finger family of genes may exist as a cluster in this region.

Animals↗
PubMed1998

[Isolation of novel expression sequences of C2H2 type zinc finger protein gene from human brain tissue according to the conservation of zinc finger motif].

By low stringency PCR amplification of genomic DNA using the primers designed based on the conservation of zinc finger motif, we got 8 gradient eletrophoretic bands. After recovery of the second and third bands, the DNA fragments in them were cloned and sequenced. Compared to the GenBank database, among these 60 segments containing zinc finger motif, 23 segments were novel zinc finger genes' genomic segments. Then the human brain tissue cDNA library was screened, using these segments as probes, and 44 positive clones were obtained. Rescreening 28 of them, we got 20 rescreened clones. All of them were sequenced and sent to the GenBank DNA database for sequence analysis, the results showed that 16 were novel C2H2 type zinc finger protein cDNA segments. The cDNA segments encoding the novel C2H2 type zinc finger proteins provide the basic materials for cloning of full length cDNA of valuable novel zinc finger protein genes.

Amino Acid Sequence↗
PubMed1997

Different contributions of three zinc fingers of transcription factor Sp1 to DNA recognition: novel binding mode of N-terminal finger 1.

To clarify binding properties of the first zinc finger of Sp1, finger 1, to GC-box DNA, two-finger mutant peptides Sp1 (zf12) and Sp1 (zf23) were created and their DNA binding characteristics have been compared with those of native three-zinc finger protein Sp1. Some gel electrophoretic experiments involving DNase I footprinting and gel mobility shift assays reveal that finger 1 is not essential to sequence-specific DNA recognition, but moderately contributes to total binding affinity and overall sequence specificity by three zinc fingers of Sp1.

Amino Acid Sequence↗
PubMed2005

Swapping of the beta-hairpin region between Sp1 and GLI zinc fingers: significant role of the beta-hairpin region in DNA binding properties of C2H2-type zinc finger peptides.

The recent design strategy of zinc finger peptides has mainly focused on the alpha-helix region, which plays a direct role in DNA recognition. On the other hand, the study of non-DNA-contacting regions is extremely scarce. By swapping the beta-hairpin regions between the Sp1 and GLI zinc fingers, in this study, we investigated how the beta-hairpin region of the C(2)H(2)-type zinc finger peptides contributes to the DNA binding properties. Surprisingly, the Sp1 mutant with the GLI-type beta-hairpin had a higher DNA binding affinity than that of the wild-type Sp1. The result of the DNase I footprinting analyses also showed the change in the DNA binding pattern. In contrast, the GLI zinc finger completely lost DNA binding ability as a result of exchanging the beta-hairpin region. These results strongly indicate that the beta-hairpin region appears to function as a scaffold and has an important effect on the DNA binding properties of the C(2)H(2)-type zinc finger peptides.

Amino Acid Sequence↗
PubMed2002

Bilateral side finger transposition flaps in the treatment of chronic postburn flexion contractures of the fingers.

The authors present a surgical method of releasing postburn flexion contracture of the finger by two separate transverse incisions and covering the skin defects by transposing two random-pattern flaps from both sides of the finger. One of the proximally based flaps was transposed from one side of the proximal phalanx and the other flap was transposed from the opposite side of the middle phalanx. Because the flaps were raised from different sides of different phalanxes, the donor sites were closed primarily. A total of 37 fingers (14 hands, 11 patients) were treated with this method. The patients were all men aged 20 to 24 years old. The mean follow-up period was 9 months. The lack of extension of the proximal interphalangeal joints of the fingers was improved by approximately 45 deg using the described method. The authors conclude that this method can be used effectively in the treatment of mild to moderate postburn flexion contractures of the fingers.

Adult↗