title: Crystal structure of human intrinsic factor: cobalamin complex at 2.6-A resolution.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: F S
authors.initials: FS
authors.lastname: Mathews
authors.forename: M M
authors.initials: MM
authors.lastname: Gordon
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
authors.forename: K R
authors.initials: KR
authors.lastname: Rajashankar
authors.forename: S E
authors.initials: SE
authors.lastname: Ealick
authors.forename: D H
authors.initials: DH
authors.lastname: Alpers
authors.forename: N
authors.initials: N
authors.lastname: Sukumar
mesh_terms: D018360:Crystallography, X-Ray; D006801:Humans; D007437:Intrinsic Factor / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D050722:Oncogene Protein v-cbl / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D055672:Static Electricity; D040681:Structural Homology, Protein; D014805:Vitamin B 12 / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D050722:Oncogene Protein v-cbl; D007437:Intrinsic Factor; D014805:Vitamin B 12