The Properties of Thyroglobulin IX. THE MOLECULAR PROPERTIES OF IODINATED THYROGLOBULIN HAROLD EDELHOCH AND R. E. LIPPOLDT

Iodine reacts readily with many proteins and has been used as a group-specific reagent to study the relationship between enzyme and group activity (see, for instance, (1, 2)) (3). Iodoprotein derivatives have also been prepared as electron dense protein crystals for use in x-ray investigations (4). At very low levels of iodination, radioactively labeled iodoproteins have been employed as tracers in lifetime studies of serum proteins (5, 6) and in other biological processes (7, 8). Although many proteins have been iodinated and used as investigative tools, few have been extensively characterized in terms of their physicochemical behavior. In a careful study of human serum albumin, Hughes and Straessle (4) were able to crystallize iodo derivatives containing up to 15 atoms of iodine per mole of albumin. In an investigation of the mobility distributions of several iodinated preparations of human serum albumin by electrophoretic boundary spreading experiments, Baldwin, Laughton, and Alberty (9) found that substitution of 7.2 iodine atoms per mole had only a relatively small effect on the mobility distribution. A considerable increase in heterogeneity was observed when 18 iodine atoms were introduced into the protein. At 40.5 atoms, the mobiity distribution was very broad and apparently only 50% of the protein was soluble. In the accompanying report (lo), the distribution of iodine in tyrosine and thyronine derivatives in native and iodinated thyroglobulins has been evaluated by spectrophotometric methods. The effects of iodination on the molecular properties of thyroglobulin have been studied by a variety of methods which depend on various aspects of its macromolecular structure and are reported herewith.