9N1S

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

Summary for 9N1S

• Entry DOI: 10.2210/pdb9n1s/pdb
• Related: 9BWA
• Descriptor: Transport and Golgi organization protein 2 homolog, PHOSPHATE ION, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: tango2, tango2-related disease, lipid transport
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 31975.36

Authors

Lovell, S.,Cooper, A.,Powers, A.,Battaile, K.P.,Moshen, A.W.,Ghaloul-Gonzalez, L. (deposition date: 2025-01-27, release date: 2025-04-30, Last modification date: 2026-01-14)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.3 Å)