A pH-dependent reversible conformational transition of the human transferrin receptor leads to self-association.
Human transferrin receptor (tfR) is a covalent homodimer of 90-kDa transmembrane subunits, which transits an endocytotic pathway involving exposure to low pH. Digestion of purified tfR at neutral pH generates a soluble noncovalent dimer of 70-kDa fragment subunits containing 95% of the extracellular tfR sequence, including the transferrin binding sites. Below pH 6, the 70-kDa fragment undergoes a conformational transition, which causes reversible association of the dimers in solution. Transferrin binding prevents both the conformational transition and the self-association. We suggest that tfR clustering in acidic compartments results from self-association due to a conformational change that is sensitive to transferrin binding. This and other observations support a concentration mechanism based on interactions between ectodomains in intracellular lumina.
Turkewitz
A P
AP
Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, Massachusetts 02138.
Schwartz
A L
AL
Harrison
S C
SC
D002402:Cathepsin D; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D046911:Macromolecular Substances; D008970:Molecular Weight; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011487:Protein Conformation; D011990:Receptors, Transferrin / Q000378:metabolism*; D014357:Trypsin
D046911:Macromolecular Substances; D011990:Receptors, Transferrin; D014357:Trypsin; D002402:Cathepsin D