4MY2: Crystal Structure Of Norrin In Fusion With Maltose Binding Protein

Citation:
Abstract
Norrin is a cysteine-rich growth factor that is required for angiogenesis in the eye, ear, brain, and female reproductive organs. It functions as an atypical Wnt ligand by specifically binding to the Frizzled 4 (Fz4) receptor. Here we report the crystal structure of Norrin, which reveals a unique dimeric structure with each monomer adopting a conserved cystine knot fold. Functional studies demonstrate that the novel Norrin dimer interface is required for Fz4 activation. Furthermore, we demonstrate that Norrin contains separate binding sites for Fz4 and for the Wnt ligand coreceptor Lrp5 (low-density lipoprotein-related protein 5) or Lrp6. Instead of inducing Fz4 dimerization, Norrin induces the formation of a ternary complex with Fz4 and Lrp5/6 by binding to their respective extracellular domains. These results provide crucial insights into the assembly and activation of the Norrin-Fz4-Lrp5/6 signaling complex.
PDB ID: 4MY2Download
MMDB ID: 115153
PDB Deposition Date: 2013/9/27
Updated in MMDB: 2013/11
Experimental Method:
x-ray diffraction
Resolution: 2.4  Å
Similar Structures:
Biological Unit for 4MY2: dimeric; determined by author and by software (PISA)
Molecular Components in 4MY2
Label Count Molecule
Proteins (2 molecules)
2
Maltose-binding Periplasmic Protein, Norrin Fusion Protein
Molecule annotation
Chemicals (2 molecules)
1
2
* Click molecule labels to explore molecular sequence information.

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