Structure and conformation of κ light chain (LC). Structure and conformation of κ light chain (LC). (a) Simplified representation of the primary structure of a normal κ LC, including a variable segment Vκ, a short Jκ segment (the variable domain is made of Vk + Jk), and a constant domain Cκ. Vκ includes three framework segments (green) and three hypervariable regions (white) termed complementarity-determining region (CDR) because they are responsible for contacting the antigen. There are four variability subgroups—VκI to VκIV—that are defined by homology sequences of the hypervariable regions. (b) Compared conformations (solvent-accessible surfaces) of LC variable domains from a case of LC deposition disease (LCDD; BLU) and a case of light-chain (AL)-amyloidosis (REC). In LCDD, unusual CDR hydrophobic residues (green) are exposed at the surface of the molecule, where they might favor LC aggregation or interaction with other hydrophobic molecules. In contrast, in amyloidogenic LC, exposed acid residues in the CDR1 (red) may be involved in LC interaction and fibril formation. CDR basic residues are shown in blue. Pierre Ronco et al. CJASN 2006;1:1342-1350 ©2006 by American Society of Nephrology