8CEG

BAR domain protein FAM92A1 essential for mitochondrial membrane remodeling

Summary for 8CEG

• Entry DOI: 10.2210/pdb8ceg/pdb
• Descriptor: CBY1-interacting BAR domain-containing protein 1 (2 entities in total)
• Functional Keywords: bar domain, mitochondria, membrane binding, lipid binding protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 51126.05

Authors

Kajander, T.,Fudo, S.,Yan, Z.,Zhao, H. (deposition date: 2023-02-01, release date: 2024-02-21, Last modification date: 2024-09-04)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.03 Å)