LOCALIZATION OF A CONFORMATIONAL ANOMALY TO FAB-MU REGION OF A MONOCLONAL IGM CRYOGLOBULIN

Abstract

The hydrodynamic (gel filtration and sedimentation) properties of an isolated [human] monoclonal Ig[immunoglobulin]M-.kappa. cryoglobulin (McE.) and 5 non-cryoglobulin cold-soluble proteins, as well as their constituent monomeric subuints and (Fc)5.mu. and Fab.mu. fragments, were compared under native and partially denaturing conditions. The cryoimmunoglobulin exhibits a significantly greater Stokes radius than the non-cryoglobulin reference proteins. This difference arises in the Fab.mu. region of the McE. molecule. When the proteins and their fragments are analyzed by circular dichroism in the far UV region, an atypical conformation is again detected in the Fab.mu. region of the cryoglobulin. This is the 1st demonstration and partial structural localization of a conformational anomaly in a monoclonal cryoimmunoglobulin.