8YRK

Tubulin-Compound KY216: stathmin-like domain complex

This is a non-PDB format compatible entry.

Summary for 8YRK

• Entry DOI: 10.2210/pdb8yrk/pdb
• Descriptor: Detyrosinated tubulin alpha-1B chain, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, GLYCEROL, ... (15 entities in total)
• Functional Keywords: inhibitor, cell cycle
• Biological source: Mus musculus (mouse); More
• Total number of polymer chains: 6
• Total formula weight: 265370.93

Authors

Xia, Y.Z.,He, X.Y. (deposition date: 2024-03-21, release date: 2025-04-02, Last modification date: 2026-04-22)

Primary citation

He, X.Y.,Liu, C.Y.,Ding, X.Y.,Lin, Q.,Leng, J.F.,Xiao, C.M.,Zang, X.,Wang, M.Y.,Yin, Y.,Kong, L.Y.,Xia, Y.Z.
KY216-tubulin complex captures VASH2 to inhibit NSCLC metastasis.
Nat Commun, 17:191-191, 2025

PubMed Abstract: Metastasis significantly impacts the mortality rate of non-small cell lung cancer (NSCLC) patients. Numerous microtubule-targeting agents (MTAs) reveal anti-metastatic efficacy, but the mechanism remains unclear. In this research, we employ KY216, a microtubule inhibitor, to generate a crystal in complex with αβ-tubulin, and illustrate that the KY216-tubulin combination binds vasohibin-2 (VASH2) to restrain NSCLC metastasis. Through crystal structure analysis, specific interaction sites between KY216 and curved tubulin are identified. KY216 decreases VASH2 levels, hindering the epithelial-mesenchymal transition (EMT) process in NSCLC. Moreover, the MTA enhances the binding of VASH2 to α-tubulin, prevents the activation of zinc finger E-box binding homolog 1 (ZEB1) by VASH2, promotes detyrosination of α-tubulin, and ultimately suppresses EMT. Additionally, KY216 elevates the levels of miR-429 to target the 3'-untranslated region (3' UTR) of VASH2 and ZEB1 transcripts and inhibits EMT, at least partially, via the miR-429/VASH2/ZEB1 axis to block NSCLC metastasis. Overall, our investigation offers valuable insights into the roles of MTAs and VASH2 in NSCLC metastasis.

PubMed: 41345086
DOI: 10.1038/s41467-025-66817-2

Experimental method

X-RAY DIFFRACTION (2.74 Å)