Molecular anatomy and the pathological expression of antibody light chains.

The structural diversity of overproduced free antibody light chains contributes to a spectrum of light chain deposition diseases,14 such as light chain amyloidosis (AL) and light chain deposition disease (LCDD); but in some patients, large quantities of the protein are produced without pathological complica-tions. These phenomena are currently not under-stood, and the relative roles of protein-specific and patient-specific factors remain a subject for discus-sion; however, as structural data accumulate, certain patterns of variation that appear to correlate with pathology are beginning to emerge. In this commentary, a brief overview of structural properties of light chains that may be related to different pathological tendencies is presented. multiple resulting in In the first study which primary structure was determined from a light chain extracted from LCDD related the amino acid sequence of protein MCM to the observed pathology. They suggested that the MCM protein forms LCDD because 1) it is less stable and 2) has more hydrophobic surface than other light chains, and 3) that its high isoelectric point (pl) contributes to its deposition on basement membranes.

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