Structural basis of transcobalamin recognition by human CD320 receptor
| LEADER | caa a22 4500 | ||
|---|---|---|---|
| 001 | 528785745 | ||
| 005 | 20190713030954.0 | ||
| 007 | cr unu---uuuuu | ||
| 008 | 180924s2016 xx s 000 0 eng | ||
| 024 | 7 | 0 | |a 10.3929/ethz-b-000118667 |2 doi |
| 024 | 7 | 0 | |a 10.1038/ncomms12100 |2 doi |
| 035 | |a (ETHRESEARCH)oai:www.research-collecti.ethz.ch:20.500.11850/118667 | ||
| 245 | 0 | 0 | |a Structural basis of transcobalamin recognition by human CD320 receptor |h [Elektronische Daten] |c [Amer Alam, Jae-Sung Woo, Jennifer Schmitz, Bernadette Prinz, Katharina Root, Fan Chen, Joël S. Bloch, Renato; id_orcid 0000-0001-5211-4358 Zenobi, Kaspar P. Locher] |
| 246 | 0 | |a Nat Commun | |
| 506 | |a Open access |2 ethresearch | ||
| 520 | 3 | |a 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. | |
| 540 | |a Creative Commons Attribution 4.0 International |u http://creativecommons.org/licenses/by/4.0 |2 ethresearch | ||
| 700 | 1 | |a Alam |D Amer |e joint author | |
| 700 | 1 | |a Woo |D Jae-Sung |e joint author | |
| 700 | 1 | |a Schmitz |D Jennifer |e joint author | |
| 700 | 1 | |a Prinz |D Bernadette |e joint author | |
| 700 | 1 | |a Root |D Katharina |e joint author | |
| 700 | 1 | |a Chen |D Fan |e joint author | |
| 700 | 1 | |a Bloch |D Joël S. |e joint author | |
| 700 | 1 | |a Zenobi |D Renato; id_orcid 0000-0001-5211-4358 |e joint author | |
| 700 | 1 | |a Locher |D Kaspar P. |e joint author | |
| 773 | 0 | |t Nature Communications |d London : Nature Publishing Group |g 7, p. 12100 |x 2041-1723 | |
| 856 | 4 | 0 | |u http://hdl.handle.net/20.500.11850/118667 |q text/html |z WWW-Backlink auf das Repository (Open access) |
| 908 | |D 1 |a Journal Article |2 ethresearch | ||
| 950 | |B ETHRESEARCH |P 856 |E 40 |u http://hdl.handle.net/20.500.11850/118667 |q text/html |z WWW-Backlink auf das Repository (Open access) | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Alam |D Amer |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Woo |D Jae-Sung |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Schmitz |D Jennifer |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Prinz |D Bernadette |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Root |D Katharina |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Chen |D Fan |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Bloch |D Joël S. |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Zenobi |D Renato; id_orcid 0000-0001-5211-4358 |e joint author | ||
| 950 | |B ETHRESEARCH |P 700 |E 1- |a Locher |D Kaspar P. |e joint author | ||
| 950 | |B ETHRESEARCH |P 773 |E 0- |t Nature Communications |d London : Nature Publishing Group |g 7, p. 12100 |x 2041-1723 | ||
| 898 | |a BK010053 |b XK010053 |c XK010000 | ||
| 949 | |B ETHRESEARCH |F ETHRESEARCH |b ETHRESEARCH |j Journal Article |c Open access | ||