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Solution structure and hydrodynamics of C. elegans UNC-6: a nematode paralogue of the vertebrate key axon guidance protein Netrin-1

DOI: 10.1016/j.bpj.2019.04.033 DOI Help

Authors: Natalie Krahn (Yale University) , Markus Meier (University of Manitoba) , Raphael Reuten (University of Copenhagen) , Manuel Koch (University of Cologne) , Joerg Stetefeld (University of Manitoba) , Trushar R. Patel (University of Lethbridge; University of Calgary; University of Alberta)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Biophysical Journal

State: Published (Approved)
Published: May 2019
Diamond Proposal Number(s): 16028

Abstract: UNC-6 (UNCoordinated-6) was the first member of the netrin family to be discovered in Caenorhabditis elegans. With homology to human netrin-1 it is a key signaling molecule involved in directing axon migration in nematodes. Similar to netrin-1, UNC-6 interacts with multiple receptors (UNC-5 and UNC-40 specifically) to guide axon migration in development. As a result of the distinct evolutionary path of UNC-6 compared to vertebrate netrins, we decided to employ an integrated approach to study its solution behavior and compare it to the high-resolution structure we previously published on vertebrate netrins. Dynamic light scattering and analytical ultracentrifugation on UNC-6 (with and without its C-domain) solubilized in a low-ionic strength buffer suggested that UNC-6 forms high-order oligomers. An increase in the buffer ionic strength resulted in a more homogeneous preparation of UNC-6, that was used for subsequent solution X-ray scattering experiments. Our biophysical analysis of UNC-6 ΔC solubilized in a high-ionic strength buffer suggested that it maintains a similar head-to-stalk arrangement as netrins -1 and -4. This phenomenon is thought to play a role in the signaling behavior of UNC-6 and its ability to move throughout the extracellular matrix.

Journal Keywords: analytical ultracentrifugation; biophysics; dynamic light scattering; UNC-6; netrin-1; small-angle X-ray scattering

Subject Areas: Biology and Bio-materials


Instruments: B21-High Throughput SAXS