Crystal structure of human intrinsic factor: Cobalamin complex at 2.6-Å resolution

F. S. Mathews, M. M. Gordon, Z. Chen, K. R. Rajashankar, S. E. Ealick, D. H. Alpers, N. Sukumar

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

The structure of intrinsic factor (IF) in complex with cobalamin (Cbl) was determined at 2.6-Å resolution. The overall fold of the molecule is that of an α66 barrel. It is a two-domain protein, and the Cbl is bound at the interface of the domains in a base-on conformation. Surprisingly, two full-length molecules, each comprising an α- and a β-domain and one Cbl, and two truncated molecules with only an α-domain are present in the same asymmetric unit. The environment around Cbl is dominated by uncharged residues, and the sixth coordinate position of Co2+ is empty. A detailed comparison between the IF-B12 complex and another Cbl transport protein complex, trans-Cbl-B12, has been made. The pH effect on the binding of Cbl analogues in transport proteins is analyzed. A possible basis for the lack of interchangeability of human and rat IF receptors is presented.

Original languageEnglish
Pages (from-to)17311-17316
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number44
DOIs
StatePublished - Oct 30 2007

Keywords

  • Cobalt
  • Glycoprotein
  • Incomplete dimer
  • Transport protein
  • X-ray

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