Frameshift PQBP-1 mutants K192Sfs*7 and R153Sfs*41 implicated in X-linked intellectual disability form stable dimers.
J Struct Biol
; 206(3): 305-313, 2019 06 01.
Article
em En
| MEDLINE
| ID: mdl-30951824
ABSTRACT
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, K192Sfs*7 and R153Sfs*41. 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.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transcrição Gênica
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Paralisia Cerebral
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Deficiência Intelectual Ligada ao Cromossomo X
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Proteínas de Ligação a DNA
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Deficiência Intelectual
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Struct Biol
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2019
Tipo de documento:
Article