5DSE

Crystal Structure of the TTC7B/Hyccin Complex

5DSE の概要

• エントリーDOI: 10.2210/pdb5dse/pdb
• 関連するPDBエントリー: 4N5C
• 分子名称: Tetratricopeptide repeat protein 7B, Hyccin (3 entities in total)
• 機能のキーワード: pi4p synthesis, protein binding
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Cytoplasm, cytosol : Q86TV6 Q9BYI3
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 257160.85

構造登録者

Wu, X.,Baskin, J.M.,Reinisch, K.M.,De Camilli, P. (登録日: 2015-09-17, 公開日: 2015-12-02, 最終更新日: 2023-12-27)

主引用文献

Baskin, J.M.,Wu, X.,Christiano, R.,Oh, M.S.,Schauder, C.M.,Gazzerro, E.,Messa, M.,Baldassari, S.,Assereto, S.,Biancheri, R.,Zara, F.,Minetti, C.,Raimondi, A.,Simons, M.,Walther, T.C.,Reinisch, K.M.,De Camilli, P.
The leukodystrophy protein FAM126A (hyccin) regulates PtdIns(4)P synthesis at the plasma membrane.
Nat.Cell Biol., 18:132-138, 2016

PubMed Abstract: Genetic defects in myelin formation and maintenance cause leukodystrophies, a group of white matter diseases whose mechanistic underpinnings are poorly understood. Hypomyelination and congenital cataract (HCC), one of these disorders, is caused by mutations in FAM126A, a gene of unknown function. We show that FAM126A, also known as hyccin, regulates the synthesis of phosphatidylinositol 4-phosphate (PtdIns(4)P), a determinant of plasma membrane identity. HCC patient fibroblasts exhibit reduced PtdIns(4)P levels. FAM126A is an intrinsic component of the plasma membrane phosphatidylinositol 4-kinase complex that comprises PI4KIIIα and its adaptors TTC7 and EFR3 (refs 5,7). A FAM126A-TTC7 co-crystal structure reveals an all-α-helical heterodimer with a large protein-protein interface and a conserved surface that may mediate binding to PI4KIIIα. Absence of FAM126A, the predominant FAM126 isoform in oligodendrocytes, destabilizes the PI4KIIIα complex in mouse brain and patient fibroblasts. We propose that HCC pathogenesis involves defects in PtdIns(4)P production in oligodendrocytes, whose specialized function requires massive plasma membrane expansion and thus generation of PtdIns(4)P and downstream phosphoinositides. Our results point to a role for FAM126A in supporting myelination, an important process in development and also following acute exacerbations in multiple sclerosis.

PubMed: 26571211
DOI: 10.1038/ncb3271

実験手法

X-RAY DIFFRACTION (2.9 Å)