6a9p

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

spinqualitylabelsall models 6a9p, resolution 2.51Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6a9p is a 8 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 2.51Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease GFAP_HUMAN Alexander disease type I;Alexander disease type II. The disease is caused by mutations affecting the gene represented in this entry. Function GFAP_HUMAN GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells. Publication Abstract from PubMed 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 2.5A 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. Crystal structure of the human glial fibrillary acidic protein 1B domain.,Kim B, Kim S, Jin MS Biochem Biophys Res Commun. 2018 Sep 18;503(4):2899-2905. doi:, 10.1016/j.bbrc.2018.08.066. Epub 2018 Aug 17. PMID:30126635 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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