Accessible intrachain disulfide bonds in hybrids of light chains.

The three-dimensional structure of the Mcg lambda-type Bence-Jones dimer crystallized in ammonium sulfate is known at 2.3-A resolution. A series of nine other human lambda-chains and two kappa-chains did not crystallize under the same conditions. After these proteins were hybridized with the Mcg light chain by the method of Peabody et al. [Biochemistry, 19, 2827 (1980)], however, crystals of six heterodimers were produced. Two of these (Mcg X Weir and Mcg X Hud) were suitable for X-ray analysis. The non-Mcg parental molecules in four of the crystallizable hybrids showed aberrant electrophoretic behavior after treatment with mild reducing agents. The results suggest that the intrachain disulfide bond in at least one domain (probably the variable domain) was susceptible to mild reductive cleavage in a significant proportion of light chains. Moreover, the loosening of the domain structure resulting from such disulfide cleavage in one parent appeared to promote the tendency of a hybrid molecule to crystallize.