8CEG

BAR domain protein FAM92A1 essential for mitochondrial membrane remodeling

8CEG の概要

• エントリーDOI: 10.2210/pdb8ceg/pdb
• 分子名称: CBY1-interacting BAR domain-containing protein 1 (2 entities in total)
• 機能のキーワード: bar domain, mitochondria, membrane binding, lipid binding protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 51126.05

構造登録者

Kajander, T.,Fudo, S.,Yan, Z.,Zhao, H. (登録日: 2023-02-01, 公開日: 2024-02-21, 最終更新日: 2024-09-04)

主引用文献

Wang, L.,Yang, Z.,Satoshi, F.,Prasanna, X.,Yan, Z.,Vihinen, H.,Chen, Y.,Zhao, Y.,He, X.,Bu, Q.,Li, H.,Zhao, Y.,Jiang, L.,Qin, F.,Dai, Y.,Zhang, N.,Qin, M.,Kuang, W.,Zhao, Y.,Jokitalo, E.,Vattulainen, I.,Kajander, T.,Zhao, H.,Cen, X.
Membrane remodeling by FAM92A1 during brain development regulates neuronal morphology, synaptic function, and cognition.
Nat Commun, 15:6209-6209, 2024

PubMed Abstract: The Bin/Amphiphysin/Rvs (BAR) domain protein FAM92A1 is a multifunctional protein engaged in regulating mitochondrial ultrastructure and ciliogenesis, but its physiological role in the brain remains unclear. Here, we show that FAM92A1 is expressed in neurons starting from embryonic development. FAM92A1 knockout in mice results in altered brain morphology and age-associated cognitive deficits, potentially due to neuronal degeneration and disrupted synaptic plasticity. Specifically, FAM92A1 deficiency impairs diverse neuronal membrane morphology, including the mitochondrial inner membrane, myelin sheath, and synapses, indicating its roles in membrane remodeling and maintenance. By determining the crystal structure of the FAM92A1 BAR domain, combined with atomistic molecular dynamics simulations, we uncover that FAM92A1 interacts with phosphoinositide- and cardiolipin-containing membranes to induce lipid-clustering and membrane curvature. Altogether, these findings reveal the physiological role of FAM92A1 in the brain, highlighting its impact on synaptic plasticity and neural function through the regulation of membrane remodeling and endocytic processes.

PubMed: 39043703
DOI: 10.1038/s41467-024-50565-w

実験手法

X-RAY DIFFRACTION (2.03 Å)