The intrinsic factor (IF)-cobalamin receptor binding site is located in the amino-terminal portion of IF

L. H. Tang, H. Chokshi, C. B. Hu, M. M. Gordon, D. H. Alpers

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Intrinsic factor has two binding sites, one each for cobalamin and for the ileal receptor recognizing the intrinsic factor-cobalamin complex. To obtain initial functional mapping of these domains, cDNAs encoding intact rat and human intrinsic factor or fragments thereof were expressed transiently in COS-1 cells or in an in vitro transcription/translation system. Deletion of as little as 12% of the amino acids from the carboxyl terminus resulted in loss of cobalamin binding activity. On the other hand, the receptor binding region of intrinsic factor appears localized to a restricted region in the amino-terminal portion of the protein. Only those transcription/translation fragments of rat or human intrinsic factor tested that contained amino acid residues 25 to 62 (out of 399) showed calcium-dependent binding to isolated kidney brush borders, the shortest sequence corresponding with 20 consecutive amino acids. In contrast, a 232-amino acid carboxyl-terminal fragment of rat intrinsic factor and 243- and 338-amino acid carboxyl-terminal fragments of human intrinsic factor showed no receptor binding activity.

Original languageEnglish
Pages (from-to)22982-22986
Number of pages5
JournalJournal of Biological Chemistry
Issue number32
StatePublished - 1992


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