@article{ffe9fc5708c24f2aae455f6a43048cc7,
title = "Mutations in the PQBP1 gene prevent its interaction with the spliceosomal protein U5-15kD",
abstract = "A loss-of-function of polyglutamine tract-binding protein 1 (PQBP1) induced by frameshift mutations is believed to cause X-linked mental retardation. However, the mechanism by which structural changes in PQBP1 lead to mental retardation is unknown. Here we present the crystal structure of a C-terminal fragment of PQBP1 in complex with the spliceosomal protein U5-15kD. The U5-15kD hydrophobic groove recognizes a YxxPxxVL motif in PQBP1, and mutations within this motif cause a loss-of-function phenotype of PQBP1 in vitro. The YxxPxxVL motif is absent in all PQBP1 frameshift mutants seen in cases of mental retardation. These results suggest a mechanism by which the loss of the YxxPxxVL motif could lead to the functional defects seen in this type of mental retardation.",
author = "Mineyuki Mizuguchi and Takayuki Obita and Tomohito Serita and Rieko Kojima and Yuko Nabeshima and Hitoshi Okazawa",
note = "Funding Information: We would like to thank Mr Takahiro Morimoto for this help with the protein purification and crystallization. This study was supported by Grants-in-Aid for Scientific Research in Innovative Areas (project numbers: 21107506, 21113003, 22110001, 22110002 and 23107710) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. A part of this work was supported by Strategic Research Program for Brain Sciences (SRPBS) and Grants-in-Aid for Scientific Research (project numbers: 21790034 and 24590049) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.",
year = "2014",
month = apr,
day = "30",
doi = "10.1038/ncomms4822",
language = "英語",
volume = "5",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Research",
}