STRUCTURE AND THERMAL-STABILITY OF THE EXTRACELLULAR FRAGMENT OF HUMAN TRANSFERRIN RECEPTOR AT EXTRACELLULAR AND ENDOSOMAL PH

Fourier transform infrared spectroscopy has been used to study the solution structure and thermal stability of the extracellular fragment of human transferrin receptor (tfRt) at extracellular and endosomal pH. At extracellular pH tfRt is composed of 56% alpha-helix, 19% beta-sheet and 14% turns. Upon acidification to endosomal pH the alpha-helical content of the protein is reduced and the beta-sheet content increased by nearly 10%. At extracellular pH, the midpoint temperature of thermal denaturation (T-m) for the loss of secondary and tertiary structure, and the formation of aggregated structures, is 71 degrees C. At endosomal pH this temperature is reduced by approximate to 15 degrees C. The apparent entropies of thermal denaturation indicate that the native structure of tfRt at endosomal pH is far more flexible than at extracellular pH.