8ceg

BAR domain protein FAM92A1 essential for mitochondrial membrane remodeling

spinqualitylabelsall models 8ceg, resolution 2.03Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8ceg is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.03Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease CBAR1_HUMAN Postaxial polydactyly type A. The disease may be caused by variants affecting the gene represented in this entry. Function CBAR1_HUMAN Acts as a positive regulator of ciliary hedgehog signaling (By similarity). Probable regulator of ciliogenesis involved in limb morphogenesis (PubMed:27528616, PubMed:30395363). In cooperation with CBY1 it is involved in the recruitment and fusion of endosomal vesicles at distal appendages during early stages of ciliogenesis (PubMed:27528616, PubMed:30395363). Plays an important role in the mitochondrial function and is essential for maintaining mitochondrial morphology and inner membrane ultrastructure (PubMed:30404948). In vitro, can generate membrane curvature through preferential interaction with negatively charged phospholipids such as phosphatidylinositol 4,5-bisphosphate and cardiolipin and hence orchestrate cristae shape (PubMed:30404948).[UniProtKB:Q8BP22] Publication Abstract from PubMed 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. Membrane remodeling by FAM92A1 during brain development regulates neuronal morphology, synaptic function, and cognition.,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 Nat Commun. 2024 Jul 23;15(1):6209. doi: 10.1038/s41467-024-50565-w. PMID:39043703 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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