7ALM
Crystal structure of human GDAP1 at 2.8 Angstrom resolution.
Summary for 7ALM
| Entry DOI | 10.2210/pdb7alm/pdb |
| Descriptor | Ganglioside-induced differentiation-associated protein 1 (2 entities in total) |
| Functional Keywords | outer mitochondrial membrane protein, charcot-marie-tooth, signaling protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 65548.88 |
| Authors | Nguyen, G.T.T.,Sutinen, A.,Raasakka, A.,Kursula, P. (deposition date: 2020-10-06, release date: 2021-02-24, Last modification date: 2024-10-23) |
| Primary citation | 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 Cited by 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: 33585569DOI: 10.3389/fmolb.2020.631232 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.8 Å) |
Structure validation
Download full validation report
