Crystal structure of human intrinsic factor: cobalamin complex at 2.6-A resolution.

Publication Type:

Journal Article


Proc Natl Acad Sci U S A, Volume 104, Issue 44, p.17311-6 (2007)


Crystallography, X-Ray, Humans, Intrinsic Factor, Models, Molecular, Oncogene Protein v-cbl, Protein Binding, Protein Structure, Quaternary, Protein Structure, Tertiary, Static Electricity, Structural Homology, Protein, Vitamin B 12


<p>The structure of intrinsic factor (IF) in complex with cobalamin (Cbl) was determined at 2.6-A resolution. The overall fold of the molecule is that of an alpha(6)/alpha(6) 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 alpha- and a beta-domain and one Cbl, and two truncated molecules with only an alpha- domain are present in the same asymmetric unit. The environment around Cbl is dominated by uncharged residues, and the sixth coordinate position of Co(2+) 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.</p>