9EF2

Cryo-EM structure of alpha5beta1 integrin in complex with NeoNectin candidate 2, open conformation

Summary for 9EF2

• Entry DOI: 10.2210/pdb9ef2/pdb
• Related: 9CKV 9DIA
• EMDB information: 47968
• Descriptor: Integrin alpha-5, Integrin beta-1, NeoNectin candidate 2, ... (9 entities in total)
• Functional Keywords: a5b1, de novo, tissue regeneration, extracellular matrix protein, signaling protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 206457.76

Authors

Werther, R.,Nguyen, A.,Estrada Alamo, K.A.,Wang, X.,Campbell, M.G. (deposition date: 2024-11-19, release date: 2025-06-18)

Primary citation

Wang, X.,Guillem-Marti, J.,Kumar, S.,Lee, D.S.,Cabrerizo-Aguado, D.,Werther, R.,Alamo, K.A.E.,Zhao, Y.T.,Nguyen, A.,Kopyeva, I.,Huang, B.,Li, J.,Hao, Y.,Li, X.,Brizuela-Velasco, A.,Murray, A.,Gerben, S.,Roy, A.,DeForest, C.A.,Springer, T.,Ruohola-Baker, H.,Cooper, J.A.,Campbell, M.G.,Manero, J.M.,Ginebra, M.P.,Baker, D.
De Novo Design of Integrin alpha 5 beta 1 Modulating Proteins to Enhance Biomaterial Properties.
Adv Mater, :e2500872-e2500872, 2025

PubMed Abstract: Integrin α5β1 is crucial for cell attachment and migration in development and tissue regeneration, and α5β1 binding proteins can have considerable utility in regenerative medicine and next-generation therapeutics. We use computational protein design to create de novo α5β1-specific modulating miniprotein binders, called NeoNectins, that bind to and stabilize the open state of α5β1. When immobilized onto titanium surfaces and throughout 3D hydrogels, the NeoNectins outperform native fibronectin (FN) and RGD peptides in enhancing cell attachment and spreading, and NeoNectin-grafted titanium implants outperformed FN- and RGD-grafted implants in animal models in promoting tissue integration and bone growth. NeoNectins should be broadly applicable for tissue engineering and biomedicine.

PubMed: 40489013
DOI: 10.1002/adma.202500872

Experimental method

ELECTRON MICROSCOPY (3.36 Å)