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dc.contributor.author
Alam, Amer
dc.contributor.author
Woo, Jae-Sung
dc.contributor.author
Schmitz, Jennifer
dc.contributor.author
Prinz, Bernadette
dc.contributor.author
Root, Katharina
dc.contributor.author
Chen, Fan
dc.contributor.author
Bloch, Joël S.
dc.contributor.author
Zenobi, Renato
dc.contributor.author
Locher, Kaspar P.
dc.date.accessioned
2018-09-12T08:42:39Z
dc.date.available
2017-06-12T09:33:02Z
dc.date.available
2018-09-12T08:42:39Z
dc.date.issued
2016
dc.identifier.issn
2041-1723
dc.identifier.other
10.1038/ncomms12100
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/118667
dc.identifier.doi
10.3929/ethz-b-000118667
dc.description.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.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Nature
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.title
Structural basis of transcobalamin recognition by human CD320 receptor
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2016-07-14
ethz.journal.title
Nature Communications
ethz.journal.volume
7
en_US
ethz.journal.abbreviated
Nat Commun
ethz.pages.start
12100
en_US
ethz.size
9 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.grant
Reaction mechanism of bacterial ABC transporters and oligosaccharyltransferase
en_US
ethz.grant
Structural and mechanistic studies of components of bacterial protein N-glycosylation pathway and of vitamin B12 transport
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.identifier.nebis
007044158
ethz.publication.place
London
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02521 - Inst. f. Molekularbiologie u. Biophysik / Inst. Molecular Biology and Biophysics::03652 - Locher, Kaspar / Locher, Kaspar
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02514 - Laboratorium für Organische Chemie / Laboratory of Organic Chemistry::03430 - Zenobi, Renato / Zenobi, Renato
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02521 - Inst. f. Molekularbiologie u. Biophysik / Inst. Molecular Biology and Biophysics::03652 - Locher, Kaspar / Locher, Kaspar
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02514 - Laboratorium für Organische Chemie / Laboratory of Organic Chemistry::03430 - Zenobi, Renato / Zenobi, Renato
ethz.grant.agreementno
146191
ethz.grant.agreementno
166672
ethz.grant.fundername
SNF
ethz.grant.fundername
SNF
ethz.grant.funderDoi
10.13039/501100001711
ethz.grant.funderDoi
10.13039/501100001711
ethz.grant.program
Projektförderung in Biologie und Medizin (Abteilung III)
ethz.grant.program
Exzellenzbeitrag in Lebenswissenschaften
ethz.date.deposited
2017-06-12T09:36:18Z
ethz.source
ECIT
ethz.identifier.importid
imp593654917572068095
ethz.ecitpid
pub:180631
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-17T08:23:27Z
ethz.rosetta.lastUpdated
2024-02-02T06:03:14Z
ethz.rosetta.versionExported
true
ethz.COinS
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