EMDB-7759: Single-Molecule 3D Image of neurexin 1 alpha by Individual Partic...

基本情報

• 登録情報: データベース: EMDB / ID: EMD-7759
• タイトル: Single-Molecule 3D Image of neurexin 1 alpha by Individual Particle Electron Tomography (No. 101)
• マップデータ: Single-Molecule 3D Image of neurexin 1 alpha by Individual Particle Electron Tomography (No. 101)

試料

• 細胞器官・細胞要素: neurexin 1 alpha

• 生物種: Bos taurus (ウシ)
• 手法: 電子線トモグラフィー法 / ネガティブ染色法 / 解像度: 15.0 Å
• データ登録者: Liu JF / Misra A / Reddy S / White MA / Ren G / Rudenko G
• 引用: ジャーナル: J Mol Biol / 年: 2018; タイトル: Structural Plasticity of Neurexin 1α: Implications for its Role as Synaptic Organizer.; 著者: Jianfang Liu / Anurag Misra / M V V V Sekhar Reddy / Mark Andrew White / Gang Ren / Gabby Rudenko / ; 要旨: α-Neurexins are synaptic organizing molecules implicated in neuropsychiatric disorders. They bind and arrange an array of different partners in the synaptic cleft. The extracellular region of neurexin 1α (n1α) contains six LNS domains (L1-L6) interspersed by three Egf-like repeats. N1α must encode highly evolved structure-function relationships in order to fit into the narrow confines of the synaptic cleft, and also recruit its large, membrane-bound partners. Internal molecular flexibility could provide a solution; however, it is challenging to delineate because currently no structural methods permit high-resolution structure determination of large, flexible, multi-domain protein molecules. To investigate the structural plasticity of n1α, in particular the conformation of domains that carry validated binding sites for different protein partners, we used a panel of structural techniques. Individual particle electron tomography revealed that the N-terminally and C-terminally tethered domains, L1 and L6, have a surprisingly limited range of conformational freedom with respect to the linear central core containing L2 through L5. A 2.8-Å crystal structure revealed an unexpected arrangement of the L2 and L3 domains. Small-angle X-ray scattering and electron tomography indicated that incorporation of the alternative splice insert SS6 relieves the restricted conformational freedom between L5 and L6, suggesting that SS6 may work as a molecular toggle. The architecture of n1α thus encodes a combination of rigid and flexibly tethered domains that are uniquely poised to work together to promote its organizing function in the synaptic cleft, and may permit allosterically regulated and/or concerted protein partner binding.

履歴

登録	2018年3月28日	-
ヘッダ(付随情報) 公開	2018年4月18日	-
マップ公開	2018年9月19日	-
更新	2018年10月24日	-
現状	2018年10月24日	処理サイト: RCSB / 状態: 公開