9BWA

Crystal structure of the Transport and Golgi Organization protein 2 Homolog (TANGO2)

9BWA の概要

• エントリーDOI: 10.2210/pdb9bwa/pdb
• 分子名称: Transport and Golgi organization protein 2 homolog, PHOSPHATE ION (3 entities in total)
• 機能のキーワード: tango2, tango2-related disease, lipid transport, transport 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: 64069.75

構造登録者

Lovell, S.,Cooper, A.,Powers, A.,Battaile, K.P.,Mohsen, A.-W.,Ghaloul-Gonzalez, L. (登録日: 2024-05-21, 公開日: 2025-04-30, 最終更新日: 2026-01-14)

主引用文献

Cooper, A.,Powers, A.,Battaile, K.P.,Mohsen, A.W.,Johnson, D.K.,Lovell, S.,Ghaloul-Gonzalez, L.
The Crystal Structure of Human Transport and Golgi Organization 2 Homolog (TANGO2) Protein Reveals an alpha beta beta alpha-Fold Arrangement.
Proteins, 94:515-528, 2026

PubMed Abstract: Transport and Golgi Organization 2 Homolog (TANGO2) protein deficiency disorder (TDD) is a rare autosomal recessive disorder characterized by multi-systemic abnormalities and significant phenotypic variability including neurodevelopmental delay, seizures, intermittent ataxia, hypothyroidism, rhabdomyolysis, life-threatening metabolic derangements, and cardiac arrhythmias. Mutations in TANGO2 result in mitochondrial dysfunction, abnormal lipid homeostasis with cardiolipin deficiency, and impaired Golgi-ER trafficking in TANGO2 patient-derived cells. Despite the wide recognition of the clinical manifestations of TDD and numerous molecular studies, the precise function of TANGO2 and the pathophysiology of TDD remain poorly understood. A computationally derived three-dimensional structure model suggested that TANGO2 adopts an αββα-fold, similar to the N-terminal nucleophile aminohydrolase (Ntn) superfamily of proteins, but the experimentally verified structure has not been available thus far. Here, we present the first crystal structure of the recombinant human TANGO2, determined at 1.70 Å resolution. The X-ray structure data confirmed its predicted tertiary fold with similarity to the Ntn-hydrolase family of proteins, and the comparative analysis of the active site architecture, including residues involved in catalysis and putative ligand binding site, suggests a potential hydrolase function. Additional examination of the common mutation sites found in TDD patients provides insight regarding their potential effect on protein structure integrity.

PubMed: 40726205
DOI: 10.1002/prot.70023

実験手法

X-RAY DIFFRACTION (1.7 Å)