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 α6/α6 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.
|Number of pages||6|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - Oct 30 2007|
- Incomplete dimer
- Transport protein