6VEL

Crystal Structure of Human E-cadherin bound by mouse monoclonal antibody 66E8Fab

Summary for 6VEL

• Entry DOI: 10.2210/pdb6vel/pdb
• Descriptor: 66E8 Fab Heavy Chain, 66E8 Fab Light Chain, Ubiquitin-like protein SMT3,Cadherin-1, ... (6 entities in total)
• Functional Keywords: ssgcid, cadherin, e-cadherin, antibody, structural genomics, seattle structural genomics center for infectious disease, cell adhesion, cell adhesion-immune system complex, cell adhesion/immune system
• Biological source: Mus musculus; More
• Total number of polymer chains: 3
• Total formula weight: 89540.77

Authors

Seattle Structural Genomics Center for Infectious Disease,Seattle Structural Genomics Center for Infectious Disease (SSGCID) (deposition date: 2020-01-02, release date: 2020-01-29, Last modification date: 2024-10-09)

Primary citation

Maker, A.,Bolejack, M.,Schecterson, L.,Hammerson, B.,Abendroth, J.,Edwards, T.E.,Staker, B.,Myler, P.J.,Gumbiner, B.M.
Regulation of multiple dimeric states of E-cadherin by adhesion activating antibodies revealed through Cryo-EM and X-ray crystallography.
Pnas Nexus, 1:pgac163-pgac163, 2022

PubMed Abstract: E-cadherin adhesion is regulated at the cell surface, a process that can be replicated by activating antibodies. We use cryo-electron microscopy (EM) and X-ray crystallography to examine functional states of the cadherin adhesive dimer. This dimer is mediated by N-terminal beta strand-swapping involving Trp2, and forms via a different transient X-dimer intermediate. X-dimers are observed in cryo-EM along with monomers and strand-swap dimers, indicating that X-dimers form stable interactions. A novel EC4-mediated dimer was also observed. Activating Fab binding caused no gross structural changes in E-cadherin monomers, but can facilitate strand swapping. Moreover, activating Fab binding is incompatible with the formation of the X-dimer. Both cryo-EM and X-ray crystallography reveal a distinctive twisted strand-swap dimer conformation caused by an outward shift in the N-terminal beta strand that may represent a strengthened state. Thus, regulation of adhesion involves changes in cadherin dimer configurations.

PubMed: 36157596
DOI: 10.1093/pnasnexus/pgac163

Experimental method

X-RAY DIFFRACTION (2.65 Å)