6FG9

Mouse SORCS2 ectodomain (sortilin related VPS10 domain containing receptor 2)

Summary for 6FG9

• Entry DOI: 10.2210/pdb6fg9/pdb
• Related: 6FFY
• Descriptor: VPS10 domain-containing receptor SorCS2, 2-acetamido-2-deoxy-beta-D-glucopyranose (2 entities in total)
• Functional Keywords: sorcs2, vps10, transport, sorting, sortilin, apoptosis
• Biological source: Mus musculus (Mouse)
• Total number of polymer chains: 2
• Total formula weight: 220663.90

Authors

Leloup, N.O.L.,Janssen, B.J.C. (deposition date: 2018-01-10, release date: 2018-08-01, Last modification date: 2024-01-17)

Primary citation

Leloup, N.,Chataigner, L.M.P.,Janssen, B.J.C.
Structural insights into SorCS2-Nerve Growth Factor complex formation.
Nat Commun, 9:2979-2979, 2018

PubMed Abstract: Signaling of SorCS receptors by proneurotrophin ligands regulates neuronal plasticity, induces apoptosis and is associated with mental disorders. The detailed structure of SorCS2 and its extracellular specificity are unresolved. Here we report crystal structures of the SorCS2-NGF complex and unliganded SorCS2 ectodomain, revealing cross-braced SorCS2 homodimers with two NGF dimers bound in a 2:4 stoichiometry. Five out of six SorCS2 domains directly contribute to dimer formation and a C-terminal membrane proximal unreported domain, with an RNA recognition motif fold, locks the dimer in an intermolecular head-to-tail interaction. The complex structure shows an altered SorCS2 conformation indicating substantial structural plasticity. Both NGF dimer chains interact exclusively with the top face of a SorCS2 β-propeller. Biophysical experiments reveal that NGF, proNGF, and proBDNF bind at this site on SorCS2. Taken together, our data reveal a structurally flexible SorCS2 receptor that employs the large β-propeller as a ligand binding platform.

PubMed: 30061605
DOI: 10.1038/s41467-018-05405-z

Experimental method

X-RAY DIFFRACTION (4.2 Å)