4BWQ

Crystal structure of U5-15kD in a complex with PQBP1

Summary for 4BWQ

• Entry DOI: 10.2210/pdb4bwq/pdb
• Related: 4BWS
• Descriptor: THIOREDOXIN-LIKE PROTEIN 4A, POLYGLUTAMINE-BINDING PROTEIN 1 (3 entities in total)
• Functional Keywords: transcription, neurodegenerative disorders
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Nucleus: P83876 O60828
• Total number of polymer chains: 8
• Total formula weight: 85397.14

Authors

Mizuguchi, M.,Obita, T.,Serita, T.,Kojima, R.,Morimoto, T.,Nabeshima, Y.,Okazawa, H. (deposition date: 2013-07-04, release date: 2014-04-30, Last modification date: 2023-12-20)

Primary citation

Mizuguchi, M.,Obita, T.,Serita, T.,Kojima, R.,Nabeshima, Y.,Okazawa, H.
Mutations in the Pqbp1 Gene Prevent its Interaction with the Spliceosomal Protein U5-15Kd.
Nat.Commun., 5:3822-, 2014

PubMed 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 U5-15 kD. The U5-15 kD 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.

PubMed: 24781215
DOI: 10.1038/NCOMMS4822

Experimental method

X-RAY DIFFRACTION (2.1 Å)