WLS/Evi-Mediated Wntの輸送と分泌の構造的基礎

Rie Nygaard¹, Jia Yu², Jonathan Kim¹

¹Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center, New York, NY 10032, USA.

Cell

|December 28, 2020

まとめ

研究者らは,そのトランスポーターWntless (WLS) に結合するWntタンパク質の構造を明らかにし,動物の発達と幹細胞再生に不可欠なWnt分泌の分子詳細を明らかにした.

科学分野:

分子生物学
発達生物学
構造生物学

背景:

Wntタンパク質は細胞の運命を制御する重要なシグナリング分子であり, 形質変異と幹細胞の再生を制御する.
Wntの分泌にはO-パルミトレイションとWntless (WLS/Evi) による輸送が必要である.

研究の目的:

WLSと複合したパルミトイロ化WNT8Aの高解像度構造を決定する.
WntがトランスポーターWLSに負荷される分子のメカニズムを解明する.

主な方法:

低温電子顕微鏡 (cryo-EM) 3.2 Åの解像度で
Wnt-WLSの相互作用と生理学的関連性を調査する生化学実験.

主要な成果:

構造は,WLSがGタンパク質結合受容体 (GPCRs) に同類する膜領域を有することを明らかにする.
Wntのヘアピンが,WLSのGPCRのような領域内の水害性穴に挿入されます.
Wntのパルミトレアート変異は,WLSの膜埋め込み領域と相互作用する.

結論:

Wnt-WLS複合体の構造は,Wntの分泌に関する分子洞察を提供します.
Wntの潜在的コンフォームスイッチは,受容細胞への転送を容易にする可能性があります.
このメカニズムは動物の体計画開発と幹細胞生物学にとって根本的なものです

キーワード:

フリズリング GPCR について Wntの分泌物信号は出ない Wntless (ウェントレス)膜タンパク質膜輸送パルミトレイション単粒子冷凍電子顕微鏡構造生物学

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