HFE is an MHC-related protein that is mutated in the iron overload disease hereditary hemochromatosis (HH). HH is the most common autosomal recessive disorder known to affect people of Northern European descent: approximately 1 in 300 Caucasian individuals have HH and 1 in 10 are carriers.
HFE binds to transferrin receptor and reduces its affinity for iron-loaded transferrin. In Pamela Bjorkman's lab at Caltech, we have determined the crystal structure at 2.6 Å resolution, which reveals the locations of the HH mutations and a patch of histidines that could be involved in pH-dependent interactions.