CSUMECH SIGNED
Cholesterol and Sugar Uptake Mechanisms
Total Cost €
0EC-Contrib. €
0Partnership
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Project "CSUMECH" data sheet
The following table provides information about the project.
| Coordinator |
AARHUS UNIVERSITET
Organization address contact info |
| Coordinator Country | Denmark [DK] |
| Total cost | 1˙499˙848 € |
| EC max contribution | 1˙499˙848 € (100%) |
| Programme |
1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC)) |
| Code Call | ERC-2014-STG |
| Funding Scheme | ERC-STG |
| Starting year | 2015 |
| Duration (year-month-day) | from 2015-07-01 to 2020-06-30 |
Partnership
Take a look of project's partnership.
| # | ||||
|---|---|---|---|---|
| 1 | AARHUS UNIVERSITET | DK (AARHUS C) | coordinator | 1˙499˙848.00 |
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Project objective
Cardiovascular disease, diabetes and cancer have a dramatic impact on modern society, and in great part are related to uptake of cholesterol and sugar. We still know surprisingly little about the molecular details of the processes that goes on in this essential part of human basic metabolism. This application addresses cholesterol and sugar transport and aim to elucidate the molecular mechanism of cholesterol and sugar uptake in humans. It moves the frontiers of the field by shifting the focus to in vitro work allowing hitherto untried structural and biochemical experiments to be performed. Cholesterol uptake from the intestine is mediated by the membrane protein NPC1L1. Despite extensive research, the molecular mechanism of NPC1L1-dependent cholesterol uptake still remains largely unknown. Facilitated sugar transport in humans is made possible by sugar transporters called GLUTs and SWEETs, and every cell possesses these sugar transport systems. For all these uptake systems structural information is sorely lacking to address important mechanistic questions to help elucidate their molecular mechanism. I will address this using a complementary set of methods founded in macromolecular crystallography and electron microscopy to determine the 3-dimensional structures of key players in these uptake systems. My unpublished preliminary results have established the feasibility of this approach. This will be followed up by biochemical characterization of the molecular mechanism in vitro and in silico. This high risk/high reward membrane protein proposal could lead to a breakthrough in how we approach human biochemical pathways that are linked to trans-membrane transport. An improved understanding of cholesterol and sugar homeostasis has tremendous potential for improving general public health, and furthermore this proposal will help to uncover general principles of endocytotic uptake and facilitated diffusion systems at the molecular level.
Publications
| year | authors and title | journal | last update |
|---|---|---|---|
| 2019 |
Bjørn P. Pedersen, David L. Stokes, Hans-Jürgen Apell The KdpFABC complex – K + transport against all odds published pages: 1-34, ISSN: 0968-7688, DOI: 10.1080/09687688.2019.1638977 |
Molecular Membrane Biology | 2020-03-05 |
| 2019 |
Peter Aasted Paulsen, Tânia F. Custódio, Bjørn Panyella Pedersen Crystal structure of the plant symporter STP10 illuminates sugar uptake mechanism in monosaccharide transporter superfamily published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-08176-9 |
Nature Communications 10/1 | 2020-03-05 |
| 2019 |
Mikael B.L. Winkler, Rune T. Kidmose, Maria Szomek, Katja Thaysen, Shaun Rawson, Stephen P. Muench, Daniel Wüstner, Bjørn Panyella Pedersen Structural Insight into Eukaryotic Sterol Transport through Niemann-Pick Type C Proteins published pages: 485-497.e18, ISSN: 0092-8674, DOI: 10.1016/j.cell.2019.08.038 |
Cell 179/2 | 2020-03-05 |
| 2019 |
Rune Thomas Kidmose, Jonathan Juhl, Poul Nissen, Thomas Boesen, Jesper Lykkegaard Karlsen, Bjørn Panyella Pedersen Namdinator – automatic molecular dynamics flexible fitting of structural models into cryo-EM and crystallography experimental maps published pages: 526-531, ISSN: 2052-2525, DOI: 10.1107/s2052252519007619 |
IUCrJ 6/4 | 2020-03-05 |
| 2017 |
Ching-Shin Huang, Bjørn Panyella Pedersen, David L. Stokes Crystal structure of the potassium-importing KdpFABC membrane complex published pages: 681-685, ISSN: 0028-0836, DOI: 10.1038/nature22970 |
Nature 546/7660 | 2019-05-28 |
| 2016 |
Khyati Kapoor, Janet S. Finer-Moore, Bjørn P. Pedersen, Laura Caboni, Andrew Waight, Roman C. Hillig, Peter Bringmann, Iring Heisler, Thomas Müller, Holger Siebeneicher, and Robert M. Stroud Mechanism of inhibition of human glucose transporter GLUT1 is conserved between cytochalasin B and phenylalanine amides published pages: , ISSN: 1091-6490, DOI: 10.1073/pnas.1603735113 |
Proc Natl Acad Sci U S A | 2019-05-24 |
| 2016 |
Pedersen BP, Gourdon P, Liu X, Karlsen JL, Nissen P. Initiating heavy-atom-based phasing by multi-dimensional molecular replacement. published pages: , ISSN: 2059-7983, DOI: 10.1107/S2059798315022482 |
Acta Crystallogr D Struct Biol. | 2019-05-24 |
| 2016 |
Lyons JA, Shahsavar A, Paulsen PA, Pedersen BP, Nissen P. Expression strategies for structural studies of eukaryotic membrane proteins. published pages: , ISSN: 0959-440X, DOI: 10.1016/j.sbi.2016.06.011 |
Curr Opin Struct Biol. | 2019-05-24 |
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