6A9P

Crystal structure of the human glial fibrillary acidic protein 1B domain

6A9P の概要

• エントリーDOI: 10.2210/pdb6a9p/pdb
• 分子名称: Glial fibrillary acidic protein (2 entities in total)
• 機能のキーワード: glial fibrillary acidic protein. gfap, intermediate filament, if, alexander disease, 1b domain, structural protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 100832.45

構造登録者

Jin, M.S.,Kim, B.,Kim, S. (登録日: 2018-07-14, 公開日: 2018-09-12, 最終更新日: 2023-11-22)

主引用文献

Kim, B.,Kim, S.,Jin, M.S.
Crystal structure of the human glial fibrillary acidic protein 1B domain
Biochem.Biophys.Res.Commun., 503:2899-2905, 2018

PubMed Abstract: Glial fibrillary acidic protein (GFAP) is a homopolymeric type III intermediate filament (IF) that plays essential roles in cell migration, mitosis, development, and signaling in astrocytes and a specific type of glial cells. Its overexpression and genetic mutations lead to abnormal IF networks and accumulation of Rosenthal fibers, which results in the fatal neurodegenerative disorder Alexander disease. Herein, we present the first crystal structure of human GFAP spanning the central coiled-coil 1B domain at 2.5 Å resolution. The domain forms a tetramer comprising two equivalent parallel coiled-coil dimers that pack together in an antiparallel manner. Its assembly is stabilized by extensive networks of intermolecular hydrogen bonds, salt bridges, and hydrophobic interactions. Furthermore, mapping of the GFAP mutations associated with Alexander disease reveals that most involve residues buried in the core of the interface, and are likely to disrupt the intermolecular interactions and/or introduce steric clashes, thereby decreasing GFAP solubility and promoting aggregation. Based on our structural analysis and previous biochemical studies, we propose that GFAP assembles in the A11 mode in which coiled-coil 1B dimers lie in close axial proximity in an antiparallel fashion to provide a stable tetrameric platform for the organization of the GFAP filament.

PubMed: 30126635
DOI: 10.1016/j.bbrc.2018.08.066

実験手法

X-RAY DIFFRACTION (2.51 Å)