A receptor binding site on intrinsic factor is located between amino acids 25-44 and interacts with other parts of the protein.
A receptor-binding region of intrinsic factor (IF) has been localized to amino acid residues 25-44 by in vitro transcription/translation studies. To further define sites within the region that are necessary for binding, the effects on binding activity of brush border membranes were tested when peptides corresponding with residues 1-44 were added to normal IF and when point mutations were made between residues 25 and 44. Both human IF and IF-cobalamin (cbl) complex bound equally to membranes. None of the peptides tested inhibited human IF or IF-cbl complex binding. Both control rat IF and rat IF that was mutated to be like human IF in residues 25-44 bound to guinea pig and rat membranes; the mutant with altered charge showed 50- to 100-fold decreased affinity. Thus, the putative receptor binding region is important, but cannot alone account for all the physiologic parameters of IF binding. Conformational changes in IF are additionally important.
Wen
J
J
Division of Gastroenterology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Gordon
M M
MM
Alpers
D H
DH
D000596:Amino Acids / Q000737:chemistry*; D000818:Animals; D001665:Binding Sites; D006801:Humans; D007437:Intrinsic Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007457:Iodine Radioisotopes; D016297:Mutagenesis, Site-Directed; D011869:Radioligand Assay; D051381:Rats
D000596:Amino Acids; D007457:Iodine Radioisotopes; D007437:Intrinsic Factor