4KKI
Crystal Structure of Haptocorrin in Complex with CNCbl
Summary for 4KKI
| Entry DOI | 10.2210/pdb4kki/pdb |
| Related | 4KKJ |
| Descriptor | Transcobalamin-1, 2-acetamido-2-deoxy-beta-D-glucopyranose, CYANOCOBALAMIN, ... (6 entities in total) |
| Functional Keywords | cobalamin transport protein, alpha6-alpha6 helical barrel, transport protein |
| Biological source | Homo sapiens (human) |
| Cellular location | Secreted: P20061 |
| Total number of polymer chains | 1 |
| Total formula weight | 56308.99 |
| Authors | Furger, E.,Frei, D.C.,Schibli, R.,Fischer, E.,Prota, A.E. (deposition date: 2013-05-06, release date: 2013-07-17, Last modification date: 2024-10-09) |
| Primary citation | Furger, E.,Frei, D.C.,Schibli, R.,Fischer, E.,Prota, A.E. Structural basis for universal corrinoid recognition by the cobalamin transport protein haptocorrin. J.Biol.Chem., 288:25466-25476, 2013 Cited by PubMed Abstract: Cobalamin (Cbl; vitamin B12) is an essential micronutrient synthesized only by bacteria. Mammals have developed a sophisticated uptake system to capture the vitamin from the diet. Cbl transport is mediated by three transport proteins: transcobalamin, intrinsic factor, and haptocorrin (HC). All three proteins have a similar overall structure but a different selectivity for corrinoids. Here, we present the crystal structures of human HC in complex with cyanocobalamin and cobinamide at 2.35 and 3.0 Å resolution, respectively. The structures reveal that many of the interactions with the corrin ring are conserved among the human Cbl transporters. However, the non-conserved residues Asn-120, Arg-357, and Asn-373 form distinct interactions allowing for stabilization of corrinoids other than Cbl. 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. 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. The stabilization of ligands by all of these interactions is reflected in higher melting temperatures of the protein-ligand complexes. 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. PubMed: 23846701DOI: 10.1074/jbc.M113.483271 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.35 Å) |
Structure validation
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