The TfR-HFE complex. The structure of the ternary complex formed by transferrin, TfR, and HFE has not yet been elucidated fully. This cartoon represents our current understanding. (A) Wild-type HFE protein, associated with β2-microglobulin, binds to TfR with high affinity and decreases binding of diferric transferrin.34(B) C282Y HFE protein does not associate with β2-microglobulin and therefore is not expressed in mature form on the cell surface, leaving TfR free to bind transferrin. (C) H63D HFE protein is expressed on the cell surface, but it does not decrease TfR affinity for transferrin to the same extent as wild-type HFE does.