9LT3

Integrin alpha-v beta-3 in complex with Trimucrin

Summary for 9LT3

• Entry DOI: 10.2210/pdb9lt3/pdb
• EMDB information: 63364
• Descriptor: Integrin alpha-V,Integrin alpha-v, Integrin beta-3, Zinc metalloproteinase/disintegrin PMMP-2, ... (9 entities in total)
• Functional Keywords: disintegrin, complex, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 245968.72

Authors

Wang, Y.T.,Chuang, W.J. (deposition date: 2025-02-05, release date: 2026-02-18, Last modification date: 2026-05-20)

Primary citation

Wang, Y.T.,Chang, Y.T.,Huang, C.H.,Liau, C.T.,Chen, C.Y.,Chuang, W.J.
Structural basis for the differential recognition of integrin alpha v beta 3 by rhodostomin and trimucrin.
Commun Biol, 9:-, 2026

PubMed Abstract: Rhodostomin (Rho) and Trimucrin (Tmu) are RGD-containing disintegrins that inhibit integrins more effectively than short RGD peptides. They differ in their linker, RGD loop, and C-terminal sequences. We determined the X-ray structure of Tmu and the cryo-EM structures of integrin αvβ3 in complex with both disintegrins. Structural analysis revealed subtle differences in binding, with both adopting a rigid backbone conformation and interacting with integrin through three cooperative binding sites. Besides the conserved RGD interface, Tmu features a cluster of basic residues in its linker, while Rho has distinct C-terminal interactions. Disintegrin binding stabilizes αvβ3 in an extended-open conformation, while the β3-Y110 residue is essential for maintaining the bent state without ligands. These findings enhance our understanding of integrin recognition and inform the development of integrin-targeted therapeutics for anti-angiogenic, anti-tumor, and anti-inflammatory applications.

PubMed: 42045602
DOI: 10.1038/s42003-026-10139-6

Experimental method

ELECTRON MICROSCOPY (2.79 Å)