8H62

Crystal structure of Internalin A from Listeria monocytogenes with human E-cadherin EC12

Summary for 8H62

• Entry DOI: 10.2210/pdb8h62/pdb
• Descriptor: Internalin A, Cadherin-1, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: internalin a cadherin bacterial invasion nanobody surface plasmon resonance isothermal titration calorimetry, cell invasion
• Biological source: Listeria monocytogenes serovar 1/2a; More
• Total number of polymer chains: 2
• Total formula weight: 73268.77

Authors

Caaveiro, J.M.M.,Nagatoish, S.,Tsumoto, K. (deposition date: 2022-10-14, release date: 2023-10-04, Last modification date: 2023-10-25)

Primary citation

Yamazaki, T.,Nagatoishi, S.,Yamawaki, T.,Nozawa, T.,Matsunaga, R.,Nakakido, M.,Caaveiro, J.M.M.,Nakagawa, I.,Tsumoto, K.
Anti-InlA single-domain antibodies that inhibit the cell invasion of Listeria monocytogenes.
J.Biol.Chem., 299:105254-105254, 2023

PubMed Abstract: Listeriosis, caused by infection with Listeria monocytogenes, is a severe disease with a high mortality rate. The L. monocytogenes virulence factor, internalin family protein InlA, which binds to the host receptor E-cadherin, is necessary to invade host cells. Here, we isolated two single-domain antibodies (VHs) that bind to InlA with picomolar affinities from an alpaca immune library using the phage display method. These InlA-specific VHs inhibited the binding of InlA to the extracellular domains of E-cadherin in vitro as shown by biophysical interaction analysis. Furthermore, we determined that the VHs inhibited the invasion of L. monocytogenes into host cells in culture. High-resolution X-ray structure analyses of the complexes of VHs with InlA revealed that the VHs bind to the same binding site as E-cadherin against InlA. We conclude that these VHs have the potential for use as drugs to treat listeriosis.

PubMed: 37716701
DOI: 10.1016/j.jbc.2023.105254

Experimental method

X-RAY DIFFRACTION (1.91 Å)