Cryo-EM structures reveal distinct apo conformations of sortilin-related receptor SORLA

Sorting-related receptor with A-type repeats (SORLA) is an important receptor for regulating normal cellular functions via protein sorting. Here, we determined the structures of the full-length SORLA and identified two distinct conformations of apo-SORLA using single-particle cryogenic electron microscopy. In contrast to homologous proteins, both monomer and dimer forms of SORLA existed in a neutral solution. Only three hydrogen bonds in the vicinity of the dimer interface implied the involvement in dimerization. The orientation of residue R490 was a key point for ligand binding. These results suggest a unique mechanism of SORLA dimerization for protein trafficking. (c) 2022 Elsevier Inc. All rights reserved.

Automated summary

In this study, the structures of full-length SORLA were determined and two distinct conformations of apo-SORLA were identified using single-particle cryogenic electron microscopy. Unlike homologous proteins, SORLA existed in both monomer and dimer forms in a neutral solution. Only three hydrogen bonds near the dimer interface were involved in dimerization, and the orientation of residue R490 played a key role in ligand binding. These findings reveal a unique mechanism of SORLA dimerization for protein trafficking.