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

Dong，Fengquan1,2; Wu，Cang3; Jiang，Weipeng4; Zhai，Maocai2; Li，Haiying1; Zhai，Liting5; Zhang，Xi6,7

2022-10-08

10.1016/j.bbrc.2022.07.009

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   Impact Factor & Quartile

0006-291X

1090-2104

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.

Apo-SorCS3 Conformation change Cryo-EM structure Dimerization

SCI

English

Others

Medical Scientific Reuter Foundation of Guangdong Province of China[A2021333] ; Shenzhen Science and Technology Innovation Commission Project[JCYJ20190808120613189] ; Shenzhen Pea-cock Program-Project Development Fund[20190904141C]

Biochemistry & Molecular Biology ; Biophysics

Biochemistry & Molecular Biology ; Biophysics

WOS:000852817200014

ACADEMIC PRESS INC ELSEVIER SCIENCE

BIOLOGY & BIOCHEMISTRY

2-s2.0-85135813394

Scopus

1.The University of Hong Kong–Shenzhen Hospital,Shenzhen,Guangdong Province,518000,China
2.Shenzhen University General Hospital,Shenzhen,Guangdong Province,518000,China
3.Southern University of Science and Technology,Shenzhen,Guangdong Province,518055,China
4.South China Hospital of Shenzhen University,Shenzhen,Guangdong Province,518111,China
5.Stanford University,Stanford,CA 94305,United States
6.Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences,Shenzhen,Guangdong Province,518055,China
7.Shenzhen People's Second Hospital,Shenzhen,Guangdong Province,518000,China

Dong，Fengquan,Wu，Cang,Jiang，Weipeng,et al. Cryo-EM structure studies of the human VPS10 domain-containing receptor SorCS3[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2022,624:89-94.

Dong，Fengquan.,Wu，Cang.,Jiang，Weipeng.,Zhai，Maocai.,Li，Haiying.,...&Zhang，Xi.(2022).Cryo-EM structure studies of the human VPS10 domain-containing receptor SorCS3.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,624,89-94.

Dong，Fengquan,et al."Cryo-EM structure studies of the human VPS10 domain-containing receptor SorCS3".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 624(2022):89-94.