Search Results

You searched for all publications:

with publication states 'Published (Approved)'

Search Again...

These results only include publications that have been reviewed and processed by Diamond Light Source. To also view papers that have not yet been processed click here.

You can use the folder icon under Actions to collate papers as required. You can then click on View Folder in the left-hand navigation to review and/or download your folder.

Exact matches
Related results

2 items found (0 items not approved), displaying all items.1

Instruments / Technical Area	Publication Details	Published	Actions
B21-High Throughput SAXS	The dynamic nature of netrin-1 and the structural basis for glycosaminoglycan fragment-induced filament formation Markus Meier , Monika Gupta , Serife Akgül , Matthew Mcdougall , Thomas Imhof , Denise Nikodemus , Raphael Reuten , Aniel Moya-Torres , Vu To , Fraser Ferens , Fabian Heide , Gay P. Padilla-Meier , Philipp Kukura , Wenming Huang , Birgit Gerisch , Matthias Mörgelin , Kate Poole , Adam Antebi , Manuel Koch , Jörg Stetefeld Nature Communications 14 DOI: 10.1038/s41467-023-36692-w Open Access Show Abstract ▼ Abstract: Netrin-1 is a bifunctional chemotropic guidance cue that plays key roles in diverse cellular processes including axon pathfinding, cell migration, adhesion, differentiation, and survival. Here, we present a molecular understanding of netrin-1 mediated interactions with glycosaminoglycan chains of diverse heparan sulfate proteoglycans (HSPGs) and short heparin oligosaccharides. Whereas interactions with HSPGs act as platform to co-localise netrin-1 close to the cell surface, heparin oligosaccharides have a significant impact on the highly dynamic behaviour of netrin-1. Remarkably, the monomer-dimer equilibrium of netrin-1 in solution is abolished in the presence of heparin oligosaccharides and replaced with highly hierarchical and distinct super assemblies leading to unique, yet unknown netrin-1 filament formation. In our integrated approach we provide a molecular mechanism for the filament assembly which opens fresh paths towards a molecular understanding of netrin-1 functions.	Mar 2023
B21-High Throughput SAXS	Heparins mediate the multimer assembly of secreted Noggin Fabian Heide , Scott Legare , Vu To , Monika Gupta , Haben Gabir , Thomas Imhof , Aniel Moya-Torres , Matthew Mcdougall , Markus Meier , Manuel Koch , Jörg Stetefeld Protein Science 31 DOI: 10.1002/pro.4419 Diamond Proposal Number(s): [22113] Show Abstract ▼ Abstract: Extracellular matrix proteins are most often defined by their direct function that involves receptor binding and subsequent downstream signaling. However, these proteins often contain structural binding regions that allow for the proper localization in the extracellular space which guides its correct function in a local and temporal manner. The regions that serve a structural function, although often associated with disease, tend to have a limited understanding. An example of this is the extracellular matrix protein Noggin; as part of the bone morphogenetic protein inhibitor family, Noggin serves a crucial regulatory function in mammalian developmental stages and later periods of life. Noggin's regular function, after its expression and extracellular release, is mediated by its retention in close proximity to the cellular surface by glycosaminoglycans, specifically heparin and heparan sulfate. Using a biophysical hybrid method approach, we present a close examination of the Noggin heparin binding interface, study its dynamic binding behaviors and observe supramolecular Noggin assemblies mediated by heparin ligands. This confirms previously suggested models of non-covalent protein assemblies mediated through glycosaminoglycans that exist in the extracellular matrix. Further, structural analyses through molecular dynamics simulations allowed us to determine contribution energies for each protein residue involved in ligand binding and correlate this to disease associated mutation data. Our combination of various biophysical and computational methods that characterize the heparin binding interface on Noggin and its protein dynamics expands on the functional understanding of Noggin and can readily be applied to other protein systems.	Sep 2022

Publications Database

Search Results

You searched for all publications:

Search Again...

Subject Areas (check all that apply) select all

Instruments used to collect data (check all that apply) select all

Collaborations involved (check all that apply) select all

Diamond Offline Facilities used

Relevant Technical Areas (check all that apply) select all

Menu for Anonymous User