8HTT

Cryo-EM structure of human TMEM87A, gluconate-bound

8HTT の概要

• エントリーDOI: 10.2210/pdb8htt/pdb
• 関連するPDBエントリー: 8HSI
• EMDBエントリー: 35017
• 分子名称: Transmembrane protein 87A,EGFP, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• 機能のキーワード: non-selective cation channel, ion channel, membrane protein, golgi-localized protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 99597.12

構造登録者

Han, A.,Kim, H.M. (登録日: 2022-12-21, 公開日: 2023-12-27, 最終更新日: 2024-11-06)

主引用文献

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

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: 38992057
DOI: 10.1038/s41467-024-49297-8

実験手法

ELECTRON MICROSCOPY (3.6 Å)