4ZRQ
E88 deletion mutant of CD320 in complex with TC2
Summary for 4ZRQ
| Entry DOI | 10.2210/pdb4zrq/pdb |
| Related | 4ZRP |
| Descriptor | Transcobalamin-2, CD320 antigen, CYANOCOBALAMIN, ... (6 entities in total) |
| Functional Keywords | ldlr-r, vitamin transporter, transport protein |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 119886.79 |
| Authors | Alam, A.,Locher, K.P. (deposition date: 2015-05-12, release date: 2016-07-20, Last modification date: 2024-10-09) |
| Primary citation | Alam, A.,Woo, J.S.,Schmitz, J.,Prinz, B.,Root, K.,Chen, F.,Bloch, J.S.,Zenobi, R.,Locher, K.P. Structural basis of transcobalamin recognition by human CD320 receptor. Nat Commun, 7:12100-12100, 2016 Cited by PubMed Abstract: Cellular uptake of vitamin B12 (cobalamin) requires capture of transcobalamin (TC) from the plasma by CD320, a ubiquitous cell surface receptor of the LDLR family. Here we present the crystal structure of human holo-TC in complex with the extracellular domain of CD320, visualizing the structural basis of the TC-CD320 interaction. The observed interaction chemistry can rationalize the high affinity of CD320 for TC and lack of haptocorrin binding. The in vitro affinity and complex stability of TC-CD320 were quantitated using a solid-phase binding assay and thermostability analysis. Stable complexes with TC were also observed for the disease-causing CD320ΔE88 mutant and for the isolated LDLR-A2 domain. We also determined the structure of the TC-CD320ΔE88 complex, which revealed only minor changes compared with the wild-type complex. Finally, we demonstrate significantly reduced in vitro affinity of TC for CD320 at low pH, recapitulating the proposed ligand release during the endocytic pathway. PubMed: 27411955DOI: 10.1038/ncomms12100 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.6 Å) |
Structure validation
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