The Laboratory of biological electron microscopy and structural biology

(dr. fei sun’s lab)



1. Structural mechanism of substrate binding and modulation for human endoplasmic reticulum protein ER44.

Redox proteins in endoplasmic reticulum

ERp44 mediates thiol-dependent retention in the early secretory pathway, forming mixed disulphides with substrate proteins through its conserved CRFS motif. We solved the crystal structure of ERp44 at a resolution of 2.6A°. Three thioredoxin domains (a,b and b') are arranged in a clover-like structure. A flexible carboxy-terminal tail turns back to the b' and a domains, shielding a hydrophobic pocket in domain b' and a hydrophobic patch around the CRFS motif in domain a. Mutational and functional studies indicate that the C-terminal tail gates the CRFS area and the adjacent hydrophobic pocket, dynamically regulating protein quality control.


Wang, L., Wang, L., Vavassori, S., Li, S., Ke, H., Anelli, T., Degano, M., Ronzoni, R., Sitia, R., Sun, F.* & Wang, C. C.* (2008) Crystal structure of human ERp44 shows a dynamic functional modulation by its carboxy-terminal tail, EMBO Rep. 9, 642-7.

2. Structural insights into the peroxidase activity and inactivation of human peroxiredoxin 4.

Prx4 (peroxiredoxin 4) is the only peroxiredoxin located in the ER (endoplasmic reticulum) and a proposed scavenger for H2O2. In this work we presented crystal structures of human Prx4 in three different redox forms and characterized the reaction features of Prx4 with H2O2. Prx4 exhibits a toroid-shaped decamer constructed of five catalytic dimers. Structural analysis revealed conformational changes around helix α2 and the C-terminal reigon with a YF motif from the partner subunit, which are required for inter-chain disulfide formation between Cys87 and Cys208, a critical step of the catalysis. The structural explanation for the restricting role of the YF motif on the active site dynamics is provided in detail. Prx4 has a high reactivity to H2O2, but is susceptible to over-oxidation and consequent inactivation by H2O2. Either deletion of the YF motif or dissociation into dimers decreased the susceptibility of Prx4 to over-oxidation by increasing the flexibility of Cys87.


Wang Xi, Wang Likun, Wang Xi's, Sun Fei* and Wang Chih-chen*. (2011), Structural insights into the peroxidase activity and inactivation of human peroxiredoxin 4. Biochem. J., 441: 113-118.

(In collaboration with Prof. Chichen Wang, IBP)