ジャーナル: Neuron / 年: 2018 タイトル: Structural Basis for Draxin-Modulated Axon Guidance and Fasciculation by Netrin-1 through DCC. 著者: Ying Liu / Tuhin Bhowmick / Yiqiong Liu / Xuefan Gao / Haydyn D T Mertens / Dmitri I Svergun / Junyu Xiao / Yan Zhang / Jia-Huai Wang / Rob Meijers / 要旨: Axon guidance involves the spatiotemporal interplay between guidance cues and membrane-bound cell-surface receptors, present on the growth cone of the axon. Netrin-1 is a prototypical guidance cue ...Axon guidance involves the spatiotemporal interplay between guidance cues and membrane-bound cell-surface receptors, present on the growth cone of the axon. Netrin-1 is a prototypical guidance cue that binds to deleted in colorectal cancer (DCC), and it has been proposed that the guidance cue Draxin modulates this interaction. Here, we present structural snapshots of Draxin/DCC and Draxin/Netrin-1 complexes, revealing a triangular relationship that affects Netrin-mediated haptotaxis and fasciculation. Draxin interacts with DCC through the N-terminal four immunoglobulin domains, and Netrin-1 through the EGF-3 domain, in the same region where DCC binds. Netrin-1 and DCC bind to adjacent sites on Draxin, which appears to capture Netrin-1 and tether it to the DCC receptor. We propose the conformational flexibility of the single-pass membrane receptor DCC is used to promote fasciculation and regulate axon guidance through concerted Netrin-1/Draxin binding. VIDEO ABSTRACT.
温度: 298 K / 手法: 蒸気拡散法, シッティングドロップ法 / pH: 4 詳細: 1.6 M AMMONIUM SULPHATE AND 0.1 M SODIUM CITRATE, AT PH 4 TO PH 5, VAPOR DIFFUSION, TEMPERATURE 298K PH範囲: 4-5
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データ収集
回折
平均測定温度: 100 K
放射光源
由来: シンクロトロン / サイト: PETRA III, EMBL c/o DESY / ビームライン: P14 (MX2) / 波長: 0.987 Å
解像度: 3.07→54.01 Å / Cor.coef. Fo:Fc: 0.908 / Cor.coef. Fo:Fc free: 0.866 / SU B: 23.425 / SU ML: 0.375 / 交差検証法: THROUGHOUT / ESU R: 0.826 / ESU R Free: 0.387 / 立体化学のターゲット値: MAXIMUM LIKELIHOOD / 詳細: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
Rfactor
反射数
%反射
Selection details
Rfree
0.271
874
4.9 %
RANDOM
Rwork
0.235
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-
-
obs
0.237
17128
99.8 %
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溶媒の処理
イオンプローブ半径: 0.8 Å / 減衰半径: 0.8 Å / VDWプローブ半径: 1.2 Å / 溶媒モデル: MASK