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Molecular insights into the WW domain of the Golabi-Ito-Hall syndrome protein PQBP1

Author:
Sudol, Marius, McDonald, Caleb B., Farooq, Amjad
Source:
FEBS letters 2012 v.586 no.17 pp. 2795-2799
ISSN:
0014-5793
Subject:
cysteine, genes, messenger RNA, missense mutation, models, transcription (genetics), tyrosine
Abstract:
The WW domain-containing PQBP1 (polyglutamine tract-binding protein 1) protein regulates mRNA processing and gene transcription. Mutations in the PQBP1 gene were reported in several X chromosome-linked intellectual disability (XLID) disorders, including Golabi-Ito-Hall (GIH) syndrome. The missense mutation in the GIH syndrome maps within a functional region of the PQBP1 protein known as the WW domain. The causative mutation of PQBP1 replaces the conserved tyrosine (Y) at position 65 within the aromatic core of the WW domain to cysteine (C), which is a chemically significant change. In this short review, we analyze structural models of the Y65C mutated and wild type WW domains of PQBP1 in order to infer potential molecular mechanisms that render the mutated PQBP1 protein inactive in terms of ligand binding and its function as a regulator of mRNA splicing.
Agid:
983913