PMID: 23846701

 

    Legend: Sugar

Title : Structural basis for universal corrinoid recognition by the cobalamin transport protein haptocorrin

Abstract :
  1. Cobalamin ( Cbl ; vitamin B12 ) is an essential micronutrient synthesized only by bacteria
  2. Mammals have developed a sophisticated uptake system to capture the vitamin from the diet
  3. Cbl transport is mediated by three transport proteins : transcobalamin , intrinsic factor , and haptocorrin ( HC )
  4. All three proteins have a similar overall structure but a different selectivity for corrinoids
  5. Here, we present the crystal structures of human HC in complex with cyanocobalamin and cobinamide at 2.35 and 3.0 Å resolution, respectively
  6. The structures reveal that many of the interactions with the corrin ring are conserved among the human Cbl transporters
  7. However, the non-conserved residues Asn-120, Arg-357, and Asn-373 form distinct interactions allowing for stabilization of corrinoids other than Cbl
  8. A central binding motif forms interactions with the e- and f-side chains of the corrin ring and is conserved in corrinoid-binding proteins of other species
  9. In addition, the α- and β-domains of HC form several unique interdomain contacts and have a higher shape complementarity than those of intrinsic factor and transcobalamin
  10. The stabilization of ligands by all of these interactions is reflected in higher melting temperatures of the protein-ligand complexes
  11. Our structural analysis offers fundamental insights into the unique binding behavior of HC and completes the picture of Cbl interaction with its three transport proteins