Title : Crystal structure of the ligand binding
domain of
netrin G2
Abstract :
- Netrin G proteins represent a small family of synaptic cell adhesion molecules related to netrins and to the polymerization domains of laminins
- Two netrin G proteins are encoded in vertebrate genomes, netrins G1 and G2 , which are known to bind the leucine-rich repeat proteins leucine-rich repeat proteins netrin G ligand ( NGL)-1 NGL )-1 and NGL-2, respectively
- Netrin G proteins share a common multi-domain architecture comprising a laminin N-terminal (LN) domain followed by three laminin epidermal growth factor-like (LE) domains and a C' region containing a glycosylphosphatidylinositol anchor
- Here, we use deletion analysis to show that the LN domain region of netrin Gs contains the binding site for NGLs to which they bind with 1:1 stoichiometry and sub-micromolar affinity
- Netrin Gs are alternatively spliced in their LE domain regions , but the binding region , the LN domain , is identical in all splice forms.
- We determined the crystal structure for a fragment comprising the LN domain and domain LE1 of netrin G2 by sulfur single-wavelength anomalous diffraction phasing and refined it to 1.8 Å resolution
- The structure reveals an overall architecture similar to that of laminin α chain LN domains but includes significant differences including a Ca(2 +) binding site in the LN domain
- These results reveal the minimal binding unit for interaction of netrin Gs with NGLs, define structural features specific to netrin Gs, and suggest that netrin G alternative splicing is not involved in NGL recognition