Stanford Advisors


All Publications


  • Cryo-EM structure reveals polymorphic ligand-bound states of IGF1R. Journal of molecular biology Zhang, X., Wei, T., Wu, C., Jiang, J., Chen, S., Hu, Y., Lu, Y., Sun, D., Zhai, L., Zhang, J., Liu, C. 2022: 167536

    Abstract

    Type 1 insulin-like growth factor receptor (IGF1R) plays an important role in regulating cellular metabolism and cell growth and has been identified as an anticancer drug target. Although previous studies have revealed some structures of IGF1R with different ligands, the continuous dynamic conformation change remains unclear. Here, we report 10 distinct structures (7.9-3.6 A) of IGF1R bound to IGF1 or insulin to reveal the polymorphic conformations of ligand-bound IGF1R. These results showed that the alpha-CT2, disulfide bond (C670-C670'), and FnIII-2 domains had the most flexible orientations for the conformational change that occurs when ligands bind to the receptor. In addition, we found one special conformation (tentatively named the diverter-switch state) in both complexes, which may be one of the apo-IGF1R forms under ligand-treatment conditions. Hence, these results illustrated the mechanism of how different ligands could bind to human IGF1R and provided a rational template for drug design.

    View details for DOI 10.1016/j.jmb.2022.167536

    View details for PubMedID 35300993

  • Cryo-EM structures reveal distinct apo conformations of sortilin-related receptor SORLA. Biochemical and biophysical research communications Zhang, X., Wu, C., Song, Z., Sun, D., Zhai, L., Liu, C. 2022; 600: 75-79

    Abstract

    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.

    View details for DOI 10.1016/j.bbrc.2022.01.108

    View details for PubMedID 35196630