+検索条件
-Structure paper
| タイトル | Structural basis of microtubule-mediated signal transduction. |
|---|---|
| ジャーナル・号・ページ | Cell, Vol. 189, Issue 2, Page 461-477.e16, Year 2026 |
| 掲載日 | 2026年1月22日 |
著者 | Sung Ryul Choi / Thorsten B Blum / Matteo Giono / Bibhas Roy / Ioannis Vakonakis / Dominic Schmid / Nicole Oelgarth / Apisha Ranganathan / Alvar D Gossert / G V Shivashankar / Alfred Zippelius / Michel O Steinmetz / ![]() |
| PubMed 要旨 | Microtubules have long been recognized as upstream mediators of intracellular signaling, but the mechanisms underlying this fundamental function remain elusive. Here, we identify the structural basis ...Microtubules have long been recognized as upstream mediators of intracellular signaling, but the mechanisms underlying this fundamental function remain elusive. Here, we identify the structural basis by which microtubules regulate the guanine nucleotide exchange factor H1 (GEFH1), a key activator of the Ras homolog family member A (RhoA) pathway. We show that specific features of the microtubule lattice bind the C1 domain of GEFH1, leading to the sequestration and inactivation of this signaling protein. Targeted mutations in C1 residues disrupt this interaction, triggering GEFH1 release and activation of RhoA-dependent immune responses. Building on this sequestration-and-release mechanism, we identify microtubule-binding C1 domains in additional signaling proteins, including other guanine nucleotide exchange factors (GEFs), kinases, a GTPase-activating protein (GAP), and a tumor suppressor, and show that microtubule-mediated regulation via C1 domains is conserved in the Ras association domain-containing protein 1A (RASSF1A). Our findings establish a structural framework for understanding how microtubules can function as spatiotemporal signal sensors, integrating and processing diverse signaling pathways to control important cellular processes. |
リンク | Cell / PubMed:41365297 |
| 手法 | EM (単粒子) / NMR (溶液) |
| 解像度 | 2.74 - 3.4 Å |
| 構造データ | EMDB-51768, PDB-9h1o: ![]() EMDB-54112: CryoEM structure of the microtubule-AKAP13 C1 domain complex ![]() PDB-9h75: |
| 化合物 | ![]() ChemComp-ZN: ![]() ChemComp-GTP: ![]() ChemComp-MG: ![]() ChemComp-GDP: ![]() ChemComp-TA1: |
| 由来 |
|
キーワード | SIGNALING PROTEIN / RhoGEF / C1 / Cytoskeleton / Complex / PROTEIN BINDING / STRUCTURE FROM CYANA 3.98.4 |
ムービー
コントローラー
構造ビューア
万見文献について



著者

リンク








homo sapiens (ヒト)
キーワード