8KB4
Cryo-EM structure of human TMEM87A A308M
Summary for 8KB4
| Entry DOI | 10.2210/pdb8kb4/pdb |
| Related | 8HSI 8HTT |
| EMDB information | 37069 |
| Descriptor | Transmembrane protein 87A,EGFP, 2-acetamido-2-deoxy-beta-D-glucopyranose, (9R,12R)-15-amino-12-hydroxy-6,12-dioxo-7,11,13-trioxa-12lambda~5~-phosphapentadecan-9-yl undecanoate (3 entities in total) |
| Functional Keywords | non-selective cation channel, ion channel, membrane protein, golgi-localized protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 1 |
| Total formula weight | 98128.72 |
| Authors | |
| Primary citation | Kang, H.,Han, A.R.,Zhang, A.,Jeong, H.,Koh, W.,Lee, J.M.,Lee, H.,Jo, H.Y.,Maria-Solano, M.A.,Bhalla, M.,Kwon, J.,Roh, W.S.,Yang, J.,An, H.J.,Choi, S.,Kim, H.M.,Lee, C.J. GolpHCat (TMEM87A), a unique voltage-dependent cation channel in Golgi apparatus, contributes to Golgi-pH maintenance and hippocampus-dependent memory. Nat Commun, 15:5830-5830, 2024 Cited by PubMed Abstract: Impaired ion channels regulating Golgi pH lead to structural alterations in the Golgi apparatus, such as fragmentation, which is found, along with cognitive impairment, in Alzheimer's disease. However, the causal relationship between altered Golgi structure and cognitive impairment remains elusive due to the lack of understanding of ion channels in the Golgi apparatus of brain cells. Here, we identify that a transmembrane protein TMEM87A, renamed Golgi-pH-regulating cation channel (GolpHCat), expressed in astrocytes and neurons that contributes to hippocampus-dependent memory. We find that GolpHCat displays unique voltage-dependent currents, which is potently inhibited by gluconate. Additionally, we gain structural insights into the ion conduction through GolpHCat at the molecular level by determining three high-resolution cryogenic-electron microscopy structures of human GolpHCat. GolpHCat-knockout mice show fragmented Golgi morphology and altered protein glycosylation and functions in the hippocampus, leading to impaired spatial memory. These findings suggest a molecular target for Golgi-related diseases and cognitive impairment. PubMed: 38992057DOI: 10.1038/s41467-024-49297-8 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.1 Å) |
Structure validation
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