7AIA

Complex of human GDAP1 with hexadecanedioic acid

これはPDB形式変換不可エントリーです。

7AIA の概要

• エントリーDOI: 10.2210/pdb7aia/pdb
• 分子名称: Ganglioside-induced differentiation-associated protein 1, GLYCEROL, ETHANOL, ... (5 entities in total)
• 機能のキーワード: homodimer, complex, mitochondria, signaling protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 66664.26

構造登録者

Nguyen, G.T.T.,Sutinen, A.,Kursula, P. (登録日: 2020-09-26, 公開日: 2021-02-24, 最終更新日: 2024-11-20)

主引用文献

Nguyen, G.T.T.,Sutinen, A.,Raasakka, A.,Muruganandam, G.,Loris, R.,Kursula, P.
Structure of the Complete Dimeric Human GDAP1 Core Domain Provides Insights into Ligand Binding and Clustering of Disease Mutations.
Front Mol Biosci, 7:631232-631232, 2020

PubMed Abstract: Charcot-Marie-Tooth disease (CMT) is one of the most common inherited neurological disorders. Despite the common involvement of ganglioside-induced differentiation-associated protein 1 (GDAP1) in CMT, the protein structure and function, as well as the pathogenic mechanisms, remain unclear. We determined the crystal structure of the complete human GDAP1 core domain, which shows a novel mode of dimerization within the glutathione S-transferase (GST) family. The long GDAP1-specific insertion forms an extended helix and a flexible loop. GDAP1 is catalytically inactive toward classical GST substrates. Through metabolite screening, we identified a ligand for GDAP1, the fatty acid hexadecanedioic acid, which is relevant for mitochondrial membrane permeability and Ca homeostasis. The fatty acid binds to a pocket next to a CMT-linked residue cluster, increases protein stability, and induces changes in protein conformation and oligomerization. The closest homologue of GDAP1, GDAP1L1, is monomeric in its full-length form. Our results highlight the uniqueness of GDAP1 within the GST family and point toward allosteric mechanisms in regulating GDAP1 oligomeric state and function.

PubMed: 33585569
DOI: 10.3389/fmolb.2020.631232

実験手法

X-RAY DIFFRACTION (2.2 Å)