ジャーナル: Elife / 年: 2020 タイトル: Structure and activation mechanism of the BBSome membrane protein trafficking complex. 著者: Sandeep K Singh / Miao Gui / Fujiet Koh / Matthew Cj Yip / Alan Brown / 要旨: Bardet-Biedl syndrome (BBS) is a currently incurable ciliopathy caused by the failure to correctly establish or maintain cilia-dependent signaling pathways. Eight proteins associated with BBS ...Bardet-Biedl syndrome (BBS) is a currently incurable ciliopathy caused by the failure to correctly establish or maintain cilia-dependent signaling pathways. Eight proteins associated with BBS assemble into the BBSome, a key regulator of the ciliary membrane proteome. We report the electron cryomicroscopy (cryo-EM) structures of the native bovine BBSome in inactive and active states at 3.1 and 3.5 Å resolution, respectively. In the active state, the BBSome is bound to an Arf-family GTPase (ARL6/BBS3) that recruits the BBSome to ciliary membranes. ARL6 recognizes a composite binding site formed by BBS1 and BBS7 that is occluded in the inactive state. Activation requires an unexpected swiveling of the β-propeller domain of BBS1, the subunit most frequently implicated in substrate recognition, which widens a central cavity of the BBSome. Structural mapping of disease-causing mutations suggests that pathogenesis results from folding defects and the disruption of autoinhibition and activation.
モデルのタイプ: OTHER 詳細: An initial map for the BBSome was generated using RELION's implementation of the stochastic gradient descent algorithm using default parameters and a mask diameter of 280 Angstrom.
タイプ: MAXIMUM LIKELIHOOD / ソフトウェア - 名称: RELION (ver. 3.0)
最終 角度割当
タイプ: MAXIMUM LIKELIHOOD / ソフトウェア - 名称: RELION (ver. 3.0)
最終 3次元分類
クラス数: 8 / ソフトウェア - 名称: RELION (ver. 3.0)
FSC曲線 (解像度の算出)
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原子モデル構築 1
詳細
During refinement, the resolution limit was set to 3.1 Angstrom. Secondary structure, Ramachandran and rotamer restraints were applied during refinement.
精密化
空間: REAL / プロトコル: OTHER / 温度因子: 43.6 / 当てはまり具合の基準: Correlation coefficient