A comparative molecular force spectroscopy study of homophilic JAM-A interactions and JAM-A interactions with reovirus attachment protein sigma1.

Vedula SR, Lim TS, Kirchner E, Guglielmi KM, Dermody TS, Stehle T, Hunziker W, Lim CT
J Mol Recognit. 2008 21 (4): 210-6

PMID: 18446885 · PMCID: PMC4827770 · DOI:10.1002/jmr.886

JAM-A belongs to a family of immunoglobulin-like proteins called junctional adhesion molecules (JAMs) that localize at epithelial and endothelial intercellular tight junctions. JAM-A is also expressed on dendritic cells, neutrophils, and platelets. Homophilic JAM-A interactions play an important role in regulating paracellular permeability and leukocyte transmigration across epithelial monolayers and endothelial cell junctions, respectively. In addition, JAM-A is a receptor for the reovirus attachment protein, sigma1. In this study, we used single molecular force spectroscopy to compare the kinetics of JAM-A interactions with itself and sigma1. A chimeric murine JAM-A/Fc fusion protein and the purified sigma1 head domain were used to probe murine L929 cells, which express JAM-A and are susceptible to reovirus infection. The bond half-life (t(1/2)) of homophilic JAM-A interactions was found to be shorter (k(off)(o) = 0.688 +/- 0.349 s(-1)) than that of sigma1/JAM-A interactions (k(off)(o) = 0.067 +/- 0.041 s(-1)). These results are in accordance with the physiological functions of JAM-A and sigma1. A short bond lifetime imparts a highly dynamic nature to homophilic JAM-A interactions for regulating tight junction permeability while stable interactions between sigma1 and JAM-A likely anchor the virus to the cell surface and facilitate viral entry.

John Wiley & Sons, Ltd

MeSH Terms (13)

Animals Cell Adhesion Molecules Kinetics L Cells Mice Microscopy, Atomic Force Multiprotein Complexes Orthoreovirus, Mammalian Protein Interaction Domains and Motifs Protein Structure, Tertiary Receptors, Cell Surface Recombinant Fusion Proteins Viral Nonstructural Proteins

Connections (1)

This publication is referenced by other Labnodes entities: