4bws
From Proteopedia
Crystal structure of the heterotrimer of PQBP1, U5-15kD and U5-52kD.
Structural highlights
Disease[PQBP1_HUMAN] X-linked intellectual deficit, Sutherland-Haan type;X-linked intellectual deficit, Golabi-Ito-Hall type;X-linked intellectual deficit, Porteous type;Hamel cerebro-palato-cardiac syndrome. The disease is caused by mutations affecting the gene represented in this entry. Function[TXN4A_HUMAN] Essential role in pre-mRNA splicing. [PQBP1_HUMAN] May suppress the ability of POU3F2 to transactivate the DRD1 gene in a POU3F2 dependent manner. Can activate transcription directly or via association with the transcription machinery. May be involved in ATXN1 mutant-induced cell death. The interaction with ATXN1 mutant reduces levels of phosphorylated RNA polymerase II large subunit.[1] [2] [3] Publication Abstract from PubMedA 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. Mutations in the PQBP1 gene prevent its interaction with the spliceosomal protein U5-15kD.,Mizuguchi M, Obita T, Serita T, Kojima R, Nabeshima Y, Okazawa H Nat Commun. 2014 Apr 30;5:3822. doi: 10.1038/ncomms4822. PMID:24781215[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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