The prion protein binds thiamine

The FEBS Journal
Rolando Perez-PineiroDavid S Wishart

Abstract

Although highly conserved throughout evolution, the exact biological function of the prion protein is still unclear. In an effort to identify the potential biological functions of the prion protein we conducted a small-molecule screening assay using the Syrian hamster prion protein [shPrP(90-232)]. The screen was performed using a library of 149 water-soluble metabolites that are known to pass through the blood-brain barrier. Using a combination of 1D NMR, fluorescence quenching and surface plasmon resonance we identified thiamine (vitamin B1) as a specific prion ligand with a binding constant of ~60 μM. Subsequent studies showed that this interaction is evolutionarily conserved, with similar binding constants being seen for mouse, hamster and human prions. Various protein construct lengths, both with and without the unstructured N-terminal region in the presence and absence of copper, were examined. This indicates that the N-terminus has no influence on the protein's ability to interact with thiamine. In addition to thiamine, the more biologically abundant forms of vitamin B1 (thiamine monophosphate and thiamine diphosphate) were also found to bind the prion protein with similar affinity. Heteronuclear NMR experiments were use...Continue Reading

References

Nov 1, 1995·Journal of Biomolecular NMR·F DelaglioA Bax
Sep 1, 1995·Journal of Biomolecular NMR·David S WishartBrian D Sykes
Jan 1, 1996·Journal of Molecular Recognition : JMR·David S GoodsellArthur J Olson
Sep 18, 1997·Proceedings of the National Academy of Sciences of the United States of America·T L JamesF E Cohen
Nov 13, 1998·Proceedings of the National Academy of Sciences of the United States of America·S B Prusiner
Mar 2, 1999·Brain : a Journal of Neurology·G AlmerH Budka
Jul 25, 2000·Journal of Molecular Biology·F TagliaviniM Salmona
Jul 5, 2001·Proceedings of the National Academy of Sciences of the United States of America·Graham S JacksonJohn Collinge
Jul 18, 2001·The Journal of General Virology·M MoudjouC La Bonnardière
Dec 20, 2002·Clinics in Laboratory Medicine·Ermias D Belay, Lawrence B Schonberger
Feb 5, 2003·Journal of Magnetic Resonance·Charles D SchwietersG Marius Clore
Mar 12, 2003·Molecular and Cellular Probes·Ales TichopadAndrea Didier
Aug 9, 2003·Journal of Medicinal Chemistry·Martin VogtherrRalph Zahn
Feb 11, 2004·Pflügers Archiv : European journal of physiology·Vadivel GanapathyPuttur D Prasad
Mar 22, 2006·Evidence-based Complementary and Alternative Medicine : ECAM·Derrick Lonsdale
May 23, 2006·Journal of Chemical Information and Modeling·Rajarshi GuhaEgon L Willighagen
Aug 8, 2006·Biochemical and Biophysical Research Communications·Simon Wing Fai MokMichael Baier
Sep 9, 2006·Brain Research Reviews·Petrea FridNatalija Popovic
Oct 20, 2006·Nature·B Caughey, Gerald S Baron
Apr 25, 2007·Biochimica Et Biophysica Acta·Laura WestergardDavid A Harris
Jun 15, 2007·Biochimica Et Biophysica Acta·Joel C Watts, David Westaway
Oct 11, 2007·The Journal of Biological Chemistry·Kil S LeeB Caughey
Dec 13, 2007·Veterinary Research·Viviana Zomosa-SignoretJean-Pierre Liautard
Oct 28, 2008·Nucleic Acids Research·David S WishartIan Forsythe
Apr 29, 2009·Journal of Computational Chemistry·Garrett M MorrisArthur J Olson
Oct 8, 2009·PloS One·Mukesh PasupuletiArtur Schmidtchen
Jan 26, 2010·Nature Neuroscience·Juliane BremerAdriano Aguzzi
Sep 30, 2010·Proceedings of the National Academy of Sciences of the United States of America·Andrew J NicollJohn Collinge

Citations

Oct 3, 2014·Metallomics : Integrated Biometal Science·Cong ZhaoWeihong Du
Aug 29, 2013·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Xuesong WangJun Lin
Mar 14, 2016·Annals of the New York Academy of Sciences·Gary E GibsonJessica Elder
Dec 30, 2014·Medical Hypotheses·Derrick Lonsdale
Jan 13, 2015·Journal of Chromatography. a·Marcela Cristina de MoraesJerson Lima da Silva
Sep 8, 2016·Chemical Research in Toxicology·Ahmet YildirimDavid van der Spoel
Jan 26, 2017·Expert Opinion on Drug Discovery·Nataraj S PagadalaRakesh Bhat
Aug 13, 2017·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Weihong DuJufei Xu
Sep 17, 2019·Biochemistry. Biokhimii︠a︡·V A AleshinV I Bunik
Sep 17, 2020·Nutrients·Federico PaceiChiara Colombo
Jan 16, 2021·Therapeutic Advances in Psychopharmacology·Michael Ott, Ursula Werneke

Related Concepts

Prions
Plasma Protein Binding Capacity
Fluorescence Spectroscopy
Thiamine Mononitrate
Protein NMR Spectroscopy
Surface Plasmon Resonance
Brain
Biological Evolution
Ligands
Magnetic Resonance Imaging

Related Feeds

Blood Brain Barrier

The blood brain barrier is a border that separates blood from cerebrospinal fluid. Discover the latest search on this highly selective semipermeable membrane here.

Blood Brain Barrier Chips

The blood brain barrier (BBB) is comprised of endothelial cells that regulate the influx and outflux of plasma concentrations. Lab-on-a-chip devices allow scientists to model diseases and mechanisms such as the passage of therapeutic antibodies across the BBB. Discover the latest research on BBB chips here.

Blood Brain Barrier Regulation in Health & Disease

The blood brain barrier is essential in regulating the movement of molecules and substances in and out of the brain. Disruption to the blood brain barrier and changes in permeability allow pathogens and inflammatory molecules to cross the barrier and may play a part in the pathogenesis of neurodegenerative disorders. Here is the latest research in this field.