PH-dependent interdomain tethers of CD1b regulate its antigen capture.

ABSTRACT: As CD1 proteins recycle between the cell surface and endosomes, they show altered receptiveness to lipid antigen loading. We hypothesized that changes in proton concentration encountered within distinct endosomal compartments influence the charge state of residues near the entrance to the CD1 groove and thereby control antigen loading. Molecular dynamic models identified flexible areas of the CD1b heavy chain in the superior and lateral walls of the A' pocket. In these same areas, residues that carry charge in a pH-dependent manner (D60, E62) were found to tether the rigid alpha1 helix to flexible areas of the alpha2 helix and the 50-60 loop. After disruption of these tethers with acid pH or mutation, we observed increased association and dissociation of lipids with CD1b and preferential p

SUBMITTER: Relloso M 

PROVIDER: S-EPMC2753602 | biostudies-literature | 2008 Jun

REPOSITORIES: biostudies-literature