8E50
Cryo-EM structure of human glycerol-3-phosphate acyltransferase 1 (GPAT1) in complex with CoA and palmitoyl-LPA
Summary for 8E50
| Entry DOI | 10.2210/pdb8e50/pdb |
| Related | 8E4Y |
| EMDB information | 27898 27899 |
| Descriptor | Glycerol-3-phosphate acyltransferase 1, mitochondrial, COENZYME A, (2R)-2-hydroxy-3-(phosphonooxy)propyl hexadecanoate (3 entities in total) |
| Functional Keywords | acyltransferase, lpa, monotopic, mitochondrial, membrane protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 88097.49 |
| Authors | Wasilko, D.J.,Johnson, Z.L.,Ammirati, M.,Chang, J.S.,Han, S.,Wu, H. (deposition date: 2022-08-19, release date: 2022-12-21, Last modification date: 2024-06-19) |
| Primary citation | Johnson, Z.L.,Ammirati, M.,Wasilko, D.J.,Chang, J.S.,Noell, S.,Foley, T.L.,Yoon, H.,Smith, K.,Asano, S.,Hales, K.,Wan, M.,Yang, Q.,Piotrowski, M.A.,Farley, K.A.,Gilbert, T.,Aschenbrenner, L.M.,Fennell, K.F.,Dutra, J.K.,Xu, M.,Guo, C.,Varghese, A.E.,Bellenger, J.,Quinn, A.,Am Ende, C.W.,West, G.M.,Griffor, M.C.,Bennett, D.,Calabrese, M.,Steppan, C.M.,Han, S.,Wu, H. Structural basis of the acyl-transfer mechanism of human GPAT1. Nat.Struct.Mol.Biol., 30:22-30, 2023 Cited by PubMed Abstract: Glycerol-3-phosphate acyltransferase (GPAT)1 is a mitochondrial outer membrane protein that catalyzes the first step of de novo glycerolipid biosynthesis. Hepatic expression of GPAT1 is linked to liver fat accumulation and the severity of nonalcoholic fatty liver diseases. Here we present the cryo-EM structures of human GPAT1 in substrate analog-bound and product-bound states. The structures reveal an N-terminal acyltransferase domain that harbors important catalytic motifs and a tightly associated C-terminal domain that is critical for proper protein folding. Unexpectedly, GPAT1 has no transmembrane regions as previously proposed but instead associates with the membrane via an amphipathic surface patch and an N-terminal loop-helix region that contains a mitochondrial-targeting signal. Combined structural, computational and functional studies uncover a hydrophobic pathway within GPAT1 for lipid trafficking. The results presented herein lay a framework for rational inhibitor development for GPAT1. PubMed: 36522428DOI: 10.1038/s41594-022-00884-7 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.67 Å) |
Structure validation
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