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Date
2016Type
- Journal Article
Citations
Cited 23 times in
Web of Science
Cited 25 times in
Scopus
ETH Bibliography
yes
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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. Show more
Permanent link
https://doi.org/10.3929/ethz-b-000118667Publication status
publishedExternal links
Journal / series
Nature CommunicationsVolume
Pages / Article No.
Publisher
Nature Publishing GroupOrganisational unit
03652 - Locher, Kaspar / Locher, Kaspar
03430 - Zenobi, Renato / Zenobi, Renato
Funding
146191 - Reaction mechanism of bacterial ABC transporters and oligosaccharyltransferase (SNF)
166672 - Structural and mechanistic studies of components of bacterial protein N-glycosylation pathway and of vitamin B12 transport (SNF)
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Show all metadata
Citations
Cited 23 times in
Web of Science
Cited 25 times in
Scopus
ETH Bibliography
yes
Altmetrics