Tauは螺旋構造の複数のチューブリンジマーに結合する

Xiao-Han Li¹, Jacob A Culver², Elizabeth Rhoades³

¹†Department of Chemistry, Yale University, New Haven, Connecticut 06520, United States.

Journal of the American Chemical Society

|July 14, 2015

まとめ

Tauタンパク質は複数のチューブリンジマーと結合し,マイクロチューブルの組立に不可欠な障害から秩序への移行を明らかにします. この発見は,タウに関する洞察を

科学分野:

生化学と分子生物学
神経科学
構造生物学

背景:

マイクロチューブル (MT) アセンブリにおけるタウタンパク質の固有機能は重要であり,その機能不全は神経変性疾患に関与しています.
タウのメカニズムの研究は,その本質的な障害とダイナミックな性質のために困難です.

研究の目的:

タウチューブリン組のステキオメトリーと構造特性を調査する.
タウがチューブリンとどのように相互作用し,潜在的にMT組立に寄与するかを理解する.

主な方法:

光相関スペクトロスコーピー (FCS) を利用した.
アクリロダンの光スクリーニングを用いた.
MT組成を阻害する条件下でタウ・チューブリン複合体を研究した.

主要な成果:

タウは,MT組立の阻害に関係なく,複数のチューブリンジマーに結合する.
タウ-チューブリン複合体内のタウのMT結合領域で観察された螺旋構造は,部分的な折りたたみを示している.
チューブリン結合の際の障害から秩序への移行が示された.

結論:

タウの固有の障害はチューブリンとMTの結合のための柔軟な支架として機能します
障害から秩序への移行は,タウ・チューブリン相互作用を媒介する重要なメカニズムです.
発見は,MTダイナミクスと神経変性におけるタウの役割のメカニズム的基礎を提供します.

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