論文 - 詳細
| RRC ID | 77332 |
|---|---|
| 著者 | Kaur G, Ren R, Hammel M, Horton JR, Yang J, Cao Y, He C, Lan F, Lan X, Blobel GA, Blumenthal RM, Zhang X, Cheng X. |
| タイトル | Allosteric autoregulation of DNA binding via a DNA-mimicking protein domain: a biophysical study of ZNF410-DNA interaction using small angle X-ray scattering. |
| ジャーナル | Nucleic Acids Res |
| Abstract |
ZNF410 is a highly-conserved transcription factor, remarkable in that it recognizes a 15-base pair DNA element but has just a single responsive target gene in mammalian erythroid cells. ZNF410 includes a tandem array of five zinc-fingers (ZFs), surrounded by uncharacterized N- and C-terminal regions. Unexpectedly, full-length ZNF410 has reduced DNA binding affinity, compared to that of the isolated DNA binding ZF array, both in vitro and in cells. AlphaFold predicts a partially-folded N-terminal subdomain that includes a 30-residue long helix, preceded by a hairpin loop rich in acidic (aspartate/glutamate) and serine/threonine residues. This hairpin loop is predicted by AlphaFold to lie against the DNA binding interface of the ZF array. In solution, ZNF410 is a monomer and binds to DNA with 1:1 stoichiometry. Surprisingly, the single best-fit model for the experimental small angle X-ray scattering profile, in the absence of DNA, is the original AlphaFold model with the N-terminal long-helix and the hairpin loop occupying the ZF DNA binding surface. For DNA binding, the hairpin loop presumably must be displaced. After combining biophysical, biochemical, bioinformatic and artificial intelligence-based AlphaFold analyses, we suggest that the hairpin loop mimics the structure and electrostatics of DNA, and provides an additional mechanism, supplementary to sequence specificity, of regulating ZNF410 DNA binding. |
| 巻・号 | 51(4) |
| ページ | 1674-1686 |
| 公開日 | 2023-2-28 |
| DOI | 10.1093/nar/gkac1274 |
| PII | 6993853 |
| PMID | 36660822 |
| PMC | PMC9976917 |
| MeSH | Amino Acid Sequence Animals Artificial Intelligence Mammals / genetics Protein Binding Protein Domains Transcription Factors* / chemistry Transcription Factors* / metabolism Zinc Fingers / genetics |
| IF | 11.502 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | HUDEP-2(RCB4557) |