8U5B

Cryo-EM structure of human claudin-4 complex with Clostridium perfringens enterotoxin C-terminal domain and sFab COP-1

Summary for 8U5B

• Entry DOI: 10.2210/pdb8u5b/pdb
• EMDB information: 41897 41915
• Descriptor: Claudin-4, Heat-labile enterotoxin B chain, COP-1 sFab Light Chain, ... (5 entities in total)
• Functional Keywords: claudin, fab, toxin, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 88986.91

Authors

Vecchio, A.J. (deposition date: 2023-09-12, release date: 2023-09-27, Last modification date: 2024-10-30)

Primary citation

Erramilli, S.K.,Dominik, P.K.,Ogbu, C.P.,Kossiakoff, A.A.,Vecchio, A.J.
Structural and biophysical insights into targeting of claudin-4 by a synthetic antibody fragment.
Commun Biol, 7:733-733, 2024

PubMed Abstract: Claudins are a 27-member family of ~25 kDa membrane proteins that integrate into tight junctions to form molecular barriers at the paracellular spaces between endothelial and epithelial cells. As the backbone of tight junction structure and function, claudins are attractive targets for modulating tissue permeability to deliver drugs or treat disease. However, structures of claudins are limited due to their small sizes and physicochemical properties-these traits also make therapy development a challenge. Here we report the development of a synthetic antibody fragment (sFab) that binds human claudin-4 and the determination of a high-resolution structure of it bound to claudin-4/enterotoxin complexes using cryogenic electron microscopy. Structural and biophysical results reveal this sFabs mechanism of select binding to human claudin-4 over other homologous claudins and establish the ability of sFabs to bind hard-to-target claudins to probe tight junction structure and function. The findings provide a framework for tight junction modulation by sFabs for tissue-selective therapies.

PubMed: 38886509
DOI: 10.1038/s42003-024-06437-6

Experimental method

ELECTRON MICROSCOPY (5.3 Å)