Steve Ealick's Research Group

Abstract:

Mathews, FS, Gordon, MM, Chen, Z, Rajashankar, KR, Ealick, SE, Alpers, DH, and Sukumar, N. Crystal structure of human intrinsic factor: Cobalamin complex at 2.6-Å resolution. Proc. Natl. Acad. Sci. U. S. A. 104:17311-17316 (2007).

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 a₆ a₆ b 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 a- and a b-domain and one Cbl, and two truncated molecules with only an a- 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.