7LER

Netrin-1 filament assembly

PDB DOI: https://doi.org/10.2210/pdb7LER/pdb

Classification: SIGNALING PROTEIN
Organism(s): Gallus gallus
Expression System: Homo sapiens
Mutation(s): No

Deposited: 2021-01-14 Released: 2022-02-23
Deposition Author(s): McDougall, M., Gupta, M., Stetefeld, J.
Funding Organization(s): Canadian Institutes of Health Research (CIHR)

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 5.99 Å
R-Value Free: 0.368
R-Value Work: 0.304
R-Value Observed: 0.384

Starting Model: experimental
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wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.4 of the entry. See complete history.

Literature

The dynamic nature of netrin-1 and the structural basis for glycosaminoglycan fragment-induced filament formation.

Meier, M., Gupta, M., Akgul, S., McDougall, M., Imhof, T., Nikodemus, D., Reuten, R., Moya-Torres, A., To, V., Ferens, F., Heide, F., Padilla-Meier, G.P., Kukura, P., Huang, W., Gerisch, B., Morgelin, M., Poole, K., Antebi, A., Koch, M., Stetefeld, J.

(2023) Nat Commun 14: 1226-1226

PubMed: 36869049 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1038/s41467-023-36692-w
Primary Citation of Related Structures:
7LER, 7LRF

PubMed 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.

Organizational Affiliation

Department of Chemistry, University of Manitoba, Winnipeg, Canada.

Macromolecule Content

Total Structure Weight: 410.86 kDa
Atom Count: 26,405
Modelled Residue Count: 3,249
Deposited Residue Count: 3,544
Unique protein chains: 1

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Netrin-1	A B C D [auth E] E [auth D] A, B, C, D [auth E], E [auth D], F, G, H	443	Gallus gallus	Mutation(s): 0 Gene Names: NTN1
UniProt
Find proteins for Q90922 (Gallus gallus) Explore Q90922 Go to UniProtKB: Q90922
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q90922
Glycosylation
Glycosylation Sites: 4	Glycosylation Focus chain A Focus chain B Focus chain C Focus chain D [auth E] Focus chain E [auth D] Focus chain F Focus chain G Focus chain H
Sequence Annotations Expand
Reference Sequence

Oligosaccharides

Help

Entity ID: 2
Molecule	Chains	Length	2D Diagram	Glycosylation	3D Interactions
alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose	I, K, M, O, Q I, K, M, O, Q, S, U, W	5		N-Glycosylation	Interactions Focus chain I Focus chain K Focus chain M Focus chain O Focus chain Q Focus chain S Focus chain U Focus chain W Interactions & Density Focus chain I Focus chain K Focus chain M Focus chain O Focus chain Q Focus chain S Focus chain U Focus chain W
Glycosylation Resources
GlyTouCan: G22768VO GlyCosmos: G22768VO GlyGen: G22768VO

Entity ID: 3
Molecule	Chains	Length	2D Diagram	Glycosylation	3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose	J, L, N, P, R J, L, N, P, R, T, V, X	2		N-Glycosylation	Interactions Focus chain J Focus chain L Focus chain N Focus chain P Focus chain R Focus chain T Focus chain V Focus chain X Interactions & Density Focus chain J Focus chain L Focus chain N Focus chain P Focus chain R Focus chain T Focus chain V Focus chain X
Glycosylation Resources
GlyTouCan: G42666HT GlyCosmos: G42666HT GlyGen: G42666HT

Small Molecules

Ligands 1 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
NAG Query on NAG Download Ideal Coordinates CCD File SDF format, chain AA [auth B] SDF format, chain BA [auth B] SDF format, chain CA [auth C] SDF format, chain DA [auth C] SDF format, chain EA [auth E] SDF format, chain FA [auth E] SDF format, chain GA [auth D] SDF format, chain HA [auth D] SDF format, chain IA [auth F] SDF format, chain JA [auth F] SDF format, chain KA [auth G] SDF format, chain LA [auth G] SDF format, chain MA [auth H] SDF format, chain NA [auth H] SDF format, chain Y [auth A] SDF format, chain Z [auth A] MOL2 format, chain AA [auth B] MOL2 format, chain BA [auth B] MOL2 format, chain CA [auth C] MOL2 format, chain DA [auth C] MOL2 format, chain EA [auth E] MOL2 format, chain FA [auth E] MOL2 format, chain GA [auth D] MOL2 format, chain HA [auth D] MOL2 format, chain IA [auth F] MOL2 format, chain JA [auth F] MOL2 format, chain KA [auth G] MOL2 format, chain LA [auth G] MOL2 format, chain MA [auth H] MOL2 format, chain NA [auth H] MOL2 format, chain Y [auth A] MOL2 format, chain Z [auth A] mmCIF format, chain AA [auth B] mmCIF format, chain BA [auth B] mmCIF format, chain CA [auth C] mmCIF format, chain DA [auth C] mmCIF format, chain EA [auth E] mmCIF format, chain FA [auth E] mmCIF format, chain GA [auth D] mmCIF format, chain HA [auth D] mmCIF format, chain IA [auth F] mmCIF format, chain JA [auth F] mmCIF format, chain KA [auth G] mmCIF format, chain LA [auth G] mmCIF format, chain MA [auth H] mmCIF format, chain NA [auth H] mmCIF format, chain Y [auth A] mmCIF format, chain Z [auth A]	AA [auth B] BA [auth B] CA [auth C] DA [auth C] EA [auth E] AA [auth B], BA [auth B], CA [auth C], DA [auth C], EA [auth E], FA [auth E], GA [auth D], HA [auth D], IA [auth F], JA [auth F], KA [auth G], LA [auth G], MA [auth H], NA [auth H], Y [auth A], Z [auth A]	2-acetamido-2-deoxy-beta-D-glucopyranose C₈ H₁₅ N O₆ OVRNDRQMDRJTHS-FMDGEEDCSA-N		Interactions Focus chain AA [auth B] Focus chain BA [auth B] Focus chain CA [auth C] Focus chain DA [auth C] Focus chain EA [auth E] Focus chain FA [auth E] Focus chain GA [auth D] Focus chain HA [auth D] Focus chain IA [auth F] Focus chain JA [auth F] Focus chain KA [auth G] Focus chain LA [auth G] Focus chain MA [auth H] Focus chain NA [auth H] Focus chain Y [auth A] Focus chain Z [auth A] Interactions & Density Focus chain AA [auth B] Focus chain BA [auth B] Focus chain CA [auth C] Focus chain DA [auth C] Focus chain EA [auth E] Focus chain FA [auth E] Focus chain GA [auth D] Focus chain HA [auth D] Focus chain IA [auth F] Focus chain JA [auth F] Focus chain KA [auth G] Focus chain LA [auth G] Focus chain MA [auth H] Focus chain NA [auth H] Focus chain Y [auth A] Focus chain Z [auth A]