Laboratory of Signal Transduction and Proteomic Profiling, Weis Center for Research, Geisinger Clinic, Danville, PA 17821, USA.
FEBS Lett. 2012 Aug 14;586(17):2795-9. doi: 10.1016/j.febslet.2012.03.041. Epub 2012 Mar 28.
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.
含 WW 结构域的 PQBP1（多聚谷氨酰胺结合蛋白 1）蛋白调节 mRNA 加工和基因转录。在几种 X 染色体连锁的智力障碍（XLID）疾病中，包括 Golabi-Ito-Hall（GIH）综合征，已报道 PQBP1 基因突变。GIH 综合征中的错义突变位于 PQBP1 蛋白的一个功能区域内，该区域称为 WW 结构域。导致发病的 PQBP1 突变将 WW 结构域芳香族核心中位置 65 的保守酪氨酸（Y）替换为半胱氨酸（C），这是一个具有化学意义的变化。在这篇简短的综述中，我们分析了 PQBP1 的 Y65C 突变和野生型 WW 结构域的结构模型，以推断潜在的分子机制，这些机制使突变的 PQBP1 蛋白在配体结合及其作为 mRNA 剪接调节剂的功能方面失活。
