Sticky fingers: zinc-fingers as protein-recognition motifs

Gamsjaeger, Roland; Liew, Chu Kong; Loughlin, Fionna E.; Crossley, Merlin; Mackay, Joel P.

doi:10.1016/j.tibs.2006.12.007

Cited by 393 publications

(332 citation statements)

References 82 publications

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“…2A) (30,31). Zinc-ribbon folds are often involved in mediating protein-protein interactions (32). A unique aspect of the Zn3 zinc-ribbon fold is a large loop that extends from the Zn3 domain structure (amino acid residues 314 -320, Fig.…”

Section: Residues Trp-318 and Thr-316mentioning

confidence: 99%

“…Importantly, the structure is entirely unrelated to the Zn1 and Zn2 domain structures and is therefore expected to have a distinct function. Zinc-ribbon folds frequently mediate protein-protein interactions (32); therefore, this is a likely role for the zinc-ribbon fold of the Zn3 domain. In the crystal structure, the C-terminal tail of the Zn3 domain forms an extensive interface between two Zn3 monomers that are related by 2-fold crystallographic symmetry (Fig.…”

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confidence: 99%

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The Zn3 Domain of Human Poly(ADP-ribose) Polymerase-1 (PARP-1) Functions in Both DNA-dependent Poly(ADP-ribose) Synthesis Activity and Chromatin Compaction

Langelier

Ruhl

Planck

et al. 2010

Journal of Biological Chemistry

152

123

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PARP-1 is involved in multiple cellular processes, including transcription, DNA repair, and apoptosis. PARP-1 attaches ADP-ribose units to target proteins, including itself as a posttranslational modification that can change the biochemical properties of target proteins and mediate recruitment of proteins to sites of poly(ADP-ribose) synthesis. Independent of its catalytic activity, PARP-1 binds to chromatin and promotes compaction affecting RNA polymerase II transcription. PARP-1 has a modular structure composed of six independent domains. Two homologous zinc fingers, Zn1 and Zn2, form the DNAbinding module. Zn1-Zn2 binding to DNA breaks triggers catalytic activity. Recently, we have identified a third zinc binding domain in PARP-1, the Zn3 domain, which is essential for DNAdependent PARP-1 activity. The crystal structure of the Zn3 domain revealed a novel zinc-ribbon fold and a homodimeric Zn3 structure that formed in the crystal lattice. Structureguided mutagenesis was used here to investigate the roles of these two features of the Zn3 domain. Our results indicate that the zinc-ribbon fold of the Zn3 domain mediates an interdomain contact crucial to assembly of the DNA-activated conformation of PARP-1. In contrast, residues located at the Zn3 dimer interface are not required for DNA-dependent activation but rather make important contributions to the chromatin compaction activity of PARP-1. Thus, the Zn3 domain has dual roles in regulating the functions of PARP-1. Poly(ADP-ribose) polymerase-1 (PARP-1)4 is a multifunctional enzyme that covalently attaches ADP-ribose to target proteins (1, 2). Using NAD ϩ as a donor, PARP-1 can polymerize multiple units of ADP-ribose to create long and branched polymers termed poly(ADP-ribose) (PAR). This post-translational modification can change the biochemical properties and cellular location of acceptor proteins. The main substrate of PARP-1 in the cell is PARP-1 itself (automodification activity), although PARP-1 also ADP-ribosylates various substrates, including core histones, histone H1, and transcription regulatory proteins (3-7). PARP-1 can bind to nucleosomes and induce chromatin compaction, an activity that is reversed by automodification of PARP-1 (8, 9). Ecdysone-and heat shockinducible "puffing" (i.e. chromatin decondensation) of specific loci in Drosophila requires PARP-1 enzymatic activity and is accompanied by the accumulation of PAR in the puffs (10). In vivo PARP-1 localizes to actively transcribed RNA polymerase II promoters (11).PARP-1 also plays important roles in DNA repair. Following DNA damage, PARP-1 is recruited to sites of DNA lesion by its ability to bind DNA strand breaks. Binding to DNA strand breaks stimulates the automodification activity of PARP-1 and could lead to recruitment of DNA repair machinery to the sites of damage through an interaction with XRCC1 (12, 13). More recent results support an alternative model whereby PARP-1 acts to protect DNA single strand breaks from being converted to more deleterious double strand breaks, until they ca...

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Section: Residues Trp-318 and Thr-316mentioning

confidence: 99%

mentioning

confidence: 99%

The Zn3 Domain of Human Poly(ADP-ribose) Polymerase-1 (PARP-1) Functions in Both DNA-dependent Poly(ADP-ribose) Synthesis Activity and Chromatin Compaction

Langelier

Ruhl

Planck

et al. 2010

Journal of Biological Chemistry

152

123

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“…1d). MYND domains facilitate protein-protein interactions and are involved in regulatory processes 21 ; most of those in F. cylindrus appear to be lineage-specific (Supplementary Information 6). Evolutionary genetic analysis of MYND-containing proteins suggests that this family has expanded within the last 30 million years (Supplementary Information 7).…”

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confidence: 99%

Evolutionary genomics of the cold-adapted diatom Fragilariopsis cylindrus

Möck

Otillar

Strauss

et al. 2017

Nature

328

303

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The Southern Ocean houses a diverse and productive community of organisms 1,2 . Unicellular eukaryotic diatoms are the main primary producers in this environment, where photosynthesis is limited by low concentrations of dissolved iron and large seasonal fluctuations in light, temperature and the extent of sea ice 3-7 . How diatoms have adapted to this extreme environment is largely unknown. Here we present insights into the genome evolution of a cold-adapted diatom from the Southern Ocean, Fragilariopsis cylindrus 8,9 , based on a comparison with temperate diatoms. We find that approximately 24.7 per cent of the diploid F. cylindrus genome consists of genetic loci with alleles that are highly divergent (15.1 megabases of the total genome size of 61.1 megabases). These divergent alleles were differentially expressed across environmental conditions, including darkness, low iron, freezing, elevated temperature and increased CO 2 . Alleles with the largest ratio of non-synonymous to synonymous nucleotide substitutions also show the most pronounced condition-dependent expression, suggesting a correlation between diversifying selection and allelic differentiation.

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“…It is also for these reasons that zinc fingers have been successfully used for the generation of artificial transcription factors and nucleases with novel specificities (12)(13)(14). Finally, zinc fingers can mediate interactions with RNA or with other proteins (15)(16)(17), and this functional diversity, although currently not well understood, may also have led to their proliferation in the genome.…”

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confidence: 99%

The Multi-zinc Finger Protein ZNF217 Contacts DNA through a Two-finger Domain

Nunez

Clifton

Funnell

et al. 2011

Journal of Biological Chemistry

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Background: Classical C2H2 zinc finger proteins generally bind DNA via a three-finger motif. Results: We have identified the DNA site recognized by ZNF217 and defined its mechanism of binding. Conclusion: Two classical C2H2 zinc fingers, rather than the typical three, are sufficient to bind an eight base pair sequence. Significance: This work broadens our understanding of DNA binding by classical zinc fingers.

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Sticky fingers: zinc-fingers as protein-recognition motifs

Cited by 393 publications

References 82 publications

The Zn3 Domain of Human Poly(ADP-ribose) Polymerase-1 (PARP-1) Functions in Both DNA-dependent Poly(ADP-ribose) Synthesis Activity and Chromatin Compaction

The Zn3 Domain of Human Poly(ADP-ribose) Polymerase-1 (PARP-1) Functions in Both DNA-dependent Poly(ADP-ribose) Synthesis Activity and Chromatin Compaction

Evolutionary genomics of the cold-adapted diatom Fragilariopsis cylindrus

The Multi-zinc Finger Protein ZNF217 Contacts DNA through a Two-finger Domain

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