SASDET6: Polyglutamine-binding protein 1 p.Lys192Serfs*7 (PQBP-1 XLID muta...

Basic information

• Entry: Database: SASBDB / ID: SASDET6

Sample

Polyglutamine-binding protein 1 p.Lys192Serfs*7 (PQBP-1 XLID mutant K192Sfs*7)

• Polyglutamine-binding protein 1 p.Lys192Serfs*7 (protein), PQBP1 K192Sfs*7, Homo sapiens

Function / homology

Function:

neuronal ribonucleoprotein granule / alternative mRNA splicing, via spliceosome / regulation of dendrite morphogenesis / cellular response to exogenous dsRNA / regulation of RNA splicing / positive regulation of type I interferon production / ribonucleoprotein complex binding / positive regulation of defense response to virus by host / activation of innate immune response / mRNA Splicing - Major Pathway / cytoplasmic stress granule / neuron projection development / double-stranded DNA binding / defense response to virus / transcription coactivator activity / nuclear body / nuclear speck / innate immune response / regulation of DNA-templated transcription / DNA binding / nucleoplasm / nucleus / cytoplasm

Domain/homology:

WW domain superfamily / WW/rsp5/WWP domain profile. / Domain with 2 conserved Trp (W) residues / WW domain

Component:

Polyglutamine-binding protein 1

• Biological species: Homo sapiens (human)
• Citation: Journal: J Struct Biol / Year: 2019; Title: Frameshift PQBP-1 mutants K192S and R153S implicated in X-linked intellectual disability form stable dimers.; Authors: Shah Kamranur Rahman / Hitoshi Okazawa / Yu Wai Chen / ; 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, 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.

Contact author

• Yu Wai Chen (King's College London)

Models

• Model #2556: ; Type: dummy / Radius of dummy atoms: 3.00 A / Chi-square value: 1.063 / P-value: 0.728804; Search similar-shape structures of this assembly by Omokage search (details)

Sample

• Sample: Name: Polyglutamine-binding protein 1 p.Lys192Serfs*7 (PQBP-1 XLID mutant K192Sfs*7); Specimen concentration: 0.73-9.20
• Buffer: Name: Phosphate-buffered saline / pH: 7.4

Entity #1182

Name: PQBP1 K192Sfs*7 / Type: protein
Description: Polyglutamine-binding protein 1 p.Lys192Serfs*7
Formula weight: 23.254 / Num. of mol.: 2 / Source: Homo sapiens / References: UniProt: O60828
Sequence:

GPMPLPVALQ TRLAKRGILK HLEPEPEEEI IAEDYDDDPV DYEATRLEGL PPSWYKVFDP SCGLPYYWNA DTDLVSWLSP HDPNSVVTKS AKKLRSSNAD AEEKLDRSHD KSDRGHDKSD RSHEKLDRGH DKSDRGHDKS DRDRERGYDK VDRERERDRE RDRDRGYDKA DREEGKERRH HRREELAPYP KSKSSKPKG

Experimental information

• Beam: Instrument name: DORIS III EMBL X33 / City: Hamburg / 国: Germany / Type of source: X-ray synchrotronSynchrotron / Wavelength: 0.124 Å / Dist. spec. to detc.: 3 mm
• Detector: Name: Pilatus 2M

Scan

Title: Polyglutamine-binding protein 1 p.Lys192Serfs*7 (PQBP-1 XLID mutant K192Sfs*7)
Measurement date: Feb 15, 2013 / Cell temperature: 10 °C / Exposure time: 0.045 sec. / Unit: 1/nm /

	Min	Max
Q	0.0813	4.1843

Distance distribution function P(R)

Sofotware P(R): GNOM 5.0 / Number of points: 1502 /

	Min	Max
Q	0.200685	4.18426
P(R) point	1	1502
R	0	13

Result

Type of curve: merged
Comments: The entry displays the EOM ensemble Rg distributions and the fit to the data of the refined ensemble. The full EOM ensemble and log file describing the associated volume fractions is available for download in the full entry zip-archive.

	Experimental	Standard	Porod
MW	43.7 kDa	43.7 kDa	-
Volume	-	-	114 nm3

	P(R)	P(R) error	Guinier	Guinier error
Forward scattering, I0	2974	11.65	2891.74	20.44
Radius of gyration, Rg	3.778 nm	0.012	3.54 nm	0.21

	Min	Max	Error
D	-	13	1
Guinier point	11	108	-