6F8F

Co-crystal structure of SPOP MATH domain and human Pdx1 fragment

6F8F の概要

• エントリーDOI: 10.2210/pdb6f8f/pdb
• 分子名称: Speckle-type POZ protein, Pancreas/duodenum homeobox protein 1 (3 entities in total)
• 機能のキーワード: ligase, nuclear, diabetes
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 17751.30

構造登録者

Ostertag, M.S.,Popowicz, G.M.,Sattler, M. (登録日: 2017-12-13, 公開日: 2018-11-28, 最終更新日: 2024-01-17)

主引用文献

Ostertag, M.S.,Messias, A.C.,Sattler, M.,Popowicz, G.M.
The Structure of the SPOP-Pdx1 Interface Reveals Insights into the Phosphorylation-Dependent Binding Regulation.
Structure, 27:327-334.e3, 2019

PubMed Abstract: Pdx1 is a transcription factor crucial for development and maintenance of a functional pancreas. It regulates insulin expression and glucose homeostasis. SPOP is an E3-ubiquitin ligase adaptor protein that binds Pdx1, thus triggering its ubiquitination and proteasomal degradation. However, the underlying mechanisms are not well understood. Here, we present the crystal structure of the SPOP-Pdx1 complex. We show that Pdx1 residues 223-233 bind to SPOP MATH domain with low micromolar affinity. The interface is extended compared to other SPOP-client proteins. Previously, Pdx1 phosphorylation has been proposed to have a regulatory function. In this respect we show that phosphorylation lowers the affinity of Pdx1 to SPOP by isothermal titration calorimetry and nuclear magnetic resonance data. Our data provide insights into a critical protein-protein interaction that regulates cellular Pdx1 levels by SPOP-mediated decay. A reduction of Pdx1 levels in β cells is linked to apoptosis and considered a hallmark of type 2 diabetes.

PubMed: 30449689
DOI: 10.1016/j.str.2018.10.005

実験手法

X-RAY DIFFRACTION (2 Å)