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.
