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-Structure paper
タイトル | Frameshift PQBP-1 mutants K192S and R153S implicated in X-linked intellectual disability form stable dimers. |
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ジャーナル・号・ページ | J Struct Biol, Vol. 206, Issue 3, Page 305-313, Year 2019 |
掲載日 | 2019年6月1日 |
著者 | Shah Kamranur Rahman / Hitoshi Okazawa / Yu Wai Chen / |
PubMed 要旨 | Polyglutamine tract-binding protein-1 (PQBP-1) is a nuclear intrinsically disordered protein playing important roles in transcriptional regulation and RNA splicing during embryonic and postembryonic ...Polyglutamine tract-binding protein-1 (PQBP-1) is a nuclear intrinsically disordered protein playing important roles in transcriptional regulation and RNA splicing during embryonic and postembryonic development. In human, its mutations lead to severe cognitive impairment known as the Renpenning syndrome, a form of X-linked intellectual disability (XLID). Here, we report a combined biophysical study of two PQBP-1 frameshift mutants, K192S and R153S. Both mutants are dimeric in solution, in contrast to the monomeric wild-type protein. These mutants contain more folded contents and have increased thermal stabilities. Using small-angle X-ray scattering data, we generated three-dimensional envelopes which revealed their overall flat shapes. We also described each mutant using an ensemble model based on a native-like initial pool with a dimeric structural core. PQBP-1 is known to repress transcription by way of interacting with the C-terminal domain of RNA polymerase II, which consists of 52 repeats of a consensus heptapeptide sequence YSPTSPS. We studied the binding of PQBP-1 variants to the labelled peptide which is phosphorylated at positions 2 and 5 (YpSPTpSPS) and found that this interaction is significantly weakened in the two mutants. |
リンク | J Struct Biol / PubMed:30951824 |
手法 | SAS (X-ray synchrotron) |
構造データ | SASDET6: SASDEU6: |
由来 |
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