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dc.contributor.author
Hou, Yaguang
dc.contributor.author
Hu, Wanhui
dc.contributor.author
Li, Xiaona
dc.contributor.author
Skinner, John J.
dc.contributor.author
Liu, Dongsheng
dc.contributor.author
Wüthrich, Kurt
dc.date.accessioned
2017-11-29T11:57:42Z
dc.date.available
2017-11-16T16:04:51Z
dc.date.available
2017-11-28T06:44:56Z
dc.date.available
2017-11-29T11:57:42Z
dc.date.issued
2017-05
dc.identifier.issn
0925-2738
dc.identifier.issn
1573-5001
dc.identifier.other
10.1007/s10858-017-0107-8
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/209581
dc.description.abstract
The amino acid 4-fluoro-l-phenylalanine (4F-Phe) was introduced at the positions of Phe6 and Phe22 in the 29-residue polypeptide hormone glucagon by expressing glucagon in E. coli in the presence of an excess of 4F-Phe. Glucagon regulates blood glucose homeostasis by interaction with the glucagon receptor (GCGR), a class B GPCR. By referencing to the 4F-Phe chemical shifts at varying D2O concentrations, the solvent exposure of the two Phe sites along the glucagon sequence was determined, showing that 4F-Phe6 was fully solvent exposed and 4F-Phe22 was only partially exposed. The incorporation of fluorine atoms in polypeptide hormones paves the way for novel studies of their interactions with membrane-spanning receptors, specifically by differentiating between effects on the solvent accessibility, the line shapes, and the chemical shifts from interactions with lipids, detergents and proteins. Studies of interactions of GCGR with ligands in solution is at this point of keen interest, given that recent crystallographic studies revealed that an apparent small molecule antagonist actually binds as an allosteric effector at a distance of ~20 Å from the orthosteric ligand binding site (Jazayeri et al., in Nature 533:274–277, 2016).
en_US
dc.language.iso
en
en_US
dc.publisher
Springer
en_US
dc.subject
19F-NMR
en_US
dc.subject
Glucagon
en_US
dc.subject
19F chemical shift
en_US
dc.subject
Solvent exposure from D2O effects
en_US
dc.title
Solvent-accessibility of discrete residue positions in the polypeptide hormone glucagon by 19F-NMR observation of 4-fluorphenylalanine
en_US
dc.type
Journal Article
dc.date.published
2017-05-15
ethz.journal.title
Journal of Biomolecular NMR
ethz.journal.volume
68
en_US
ethz.journal.issue
1
en_US
ethz.journal.abbreviated
J. biomol. NMR
ethz.pages.start
1
en_US
ethz.pages.end
6
en_US
ethz.publication.place
Dordrecht
en_US
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::03129 - Wüthrich, Kurt / Wüthrich, Kurt
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::03129 - Wüthrich, Kurt / Wüthrich, Kurt
en_US
ethz.date.deposited
2017-11-16T16:04:54Z
ethz.source
FORM
ethz.eth
yes
en_US
ethz.availability
Metadata only
en_US
ethz.rosetta.installDate
2017-11-28T06:45:05Z
ethz.rosetta.lastUpdated
2018-11-06T04:26:05Z
ethz.rosetta.exportRequired
true
ethz.rosetta.versionExported
true
ethz.COinS
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