Computational Modeling of Claudin Structure and Function

Abstract

Tight junctions form a barrier to control passive transport of ions and small molecules across epithelia and endothelia. In addition to forming a barrier, some of claudins control transport properties of tight junctions by forming charge- and size-selective ion channels. It has been suggested claudin monomers can form or incorporate into tight junction strands to form channels. Resolving the crystallographic structure of several claudins in recent years has provided an opportunity to examine structural basis of claudins in tight junctions. Computational and theoretical modeling relying on atomic description of the pore have contributed significantly to our understanding of claudin pores and paracellular transport. In this paper, we review recent computational and mathematical modeling of claudin barrier function. We focus on dynamic modeling of global epithelial barrier function as a function of claudin pores and molecular dynamics studies of claudins leading to a functional model of claudin channels.

Interactive effect of dietary calcium and phytase on broilers challenged with subclinical necrotic enteritis: part 2. Gut permeability, phytate ester concentrations, jejunal gene expression, and intestinal morphology

“…In this study, the NE challenge led to the upregulation of the expression of the claudins (CLDN1 and CLDN5) but downregulated the expression of OCLD. Claudins determine the permeability of the space between 2 adjacent cells ( Fuladi et al., 2020 ). Therefore, a higher expression of claudins in the current study is an indication of a response of the birds to try to repair the damage that was evident because of the increased FITC-d.…”

Special Issue on “The Tight Junction and Its Proteins: More than Just a Barrier”

“…In this Special Issue, an overview is given over the molecular structures of TJ proteins published to date, focusing also on structural motifs and the types of interactions between TJ proteins and their ligands involving these motifs [ 15 ]. The resolution of such structural features of TJ proteins may further be used to model interactions and to suggest the organization of these proteins to form TJ strands with dynamic barrier- and channel-forming properties [ 16 ]. The understanding of such interactions and motifs may furthermore allow the specification and development of new compounds targeting TJs.…”

Chimeric Claudins: A New Tool to Study Tight Junction Structure and Function

“…Full-length CLDNs have been crystallized from detergent-solubilized recombinant proteins [ 10 ]. All the structures reported so far depict a monomeric structure although structural information has been extracted [ 10 ] and further used for in silico studies [ 26 ] in order to learn more of the TJ assembly, structure and function. Detergents are limited in their ability to maintain the natural oligomeric states of membrane proteins [ 27 , 28 ].…”

“…The basis for the lack of Cis- and Trans-interactions could be due to use of detergents appearing to disrupt key protein–lipid or protein–protein interactions fostered within the microenvironment of the membrane [ 40 , 41 ]. CLDN assembly in strands has been studied in silico (reviewed by Fuladi and colleagues [ 26 ]). Thus, the tertiary and quaternary structure of CLDNs remain theoretical, based almost entirely on in silico modeling [ 26 , 42 , 43 ].…”

“…CLDN assembly in strands has been studied in silico (reviewed by Fuladi and colleagues [ 26 ]). Thus, the tertiary and quaternary structure of CLDNs remain theoretical, based almost entirely on in silico modeling [ 26 , 42 , 43 ]. In particular, Fuladi et al propose that some of the in silico models are not compatible with experimental studies [ 26 ].…”