Cryo-EM structure studies of the human VPS10 domain-containing receptor SorCS3

The human VPS10 domain-containing receptor SorCS3 belongs to the Vps10p-domain receptor family and is an important receptor for regulating normal cellular functions via protein sorting. Here, we determined the cryo-EM structure of the full-length SorCS3 receptor and further found that there were at least three distinct conformations (monomer, M-shaped dimer and N-shaped dimer) of SorCS3 in the apo state. The differences between the two dimer conformations were caused by PKD1-2 assembly. In contrast to its homologous proteins, the conserved residues GLN198, ARG678, TYR430, GLU1020 and ASP1024 may be key points for its dimerization and for protein/polypeptide binding. These results showed the structural details of apo-SorCS3, which provides a foundation for elucidating the mechanism of protein sorting. (c) 2022 Elsevier Inc. All rights reserved.

Automated summary

This study determined the structural details of the human VPS10 domain-containing receptor SorCS3 and identified at least three distinct conformations in its apo state. Conserved amino acid residues may play key roles in its dimerization and protein/polypeptide binding, differentiating it from homologous proteins.