The Laboratory of biological electron microscopy and structural biology

(dr. fei sun’s lab)



1. Structural characterization of COPI in its cytosolic state.

Structural and functional study of COPI  - coat protein system for vesicle traffic from Golgi to ER

Studies on Coat Protein I (COPI) have contributed to a basic understanding of how coat proteins generate vesicles to initiate intracellular transport. The core component of the COPI complex is coatomer, which is a multimeric complex that needs to be recruited from the cytosol to membrane in order to function in membrane bending and cargo sorting.  Previous structural studies on the clathrin adaptors have found that membrane recruitment induces a large conformational change in promoting their role in cargo sorting. Here, pursuing negative-stain electron microscopy coupled with single-particle analyses, and also performing CXMS (chemical cross-linking coupled with mass spectrometry) for validation, we have reconstructed the structure of coatomer in its soluble form. When compared to the previously elucidated structure of coatomer in its membrane-bound form we do not observe a large conformational change. Thus, the result uncovers a key difference between how COPI versus clathrin coats are regulated by membrane recruitment.


Wang S., Zhai Y., Pang X., Niu T., Ding Y.H., Dong, M.Q., Hsu W.V. Sun Z.* and Sun F.* (2016), Structural characterization of coatomer in its cytosolic state. Proten Cell 7(8): 586-600. doi: 10.1007/s13238-016-0296-z

(In collaboration with Prof. Victor Hsu, Harvard Medical School)

A working model for the membrane recruitment of coatomers in promoting COPI vesicle formation. The two subcomplexes (B-subcomplex in gray and F-subcomplex in green) of coatomer can oscillate in its cytosolic state. In the absence of ARF1-GTP (magenta), coatomer binds to membrane (brown) via the B-subcomplex, remodeling the membrane into tubules or “beads-on-string” morphology, for which the precise mechanism remains to be elucidated. Oscillation of the membrane-bound coatomer prevents its ability to drive vesicle formation. In the presence of membrane-anchored ARF1-GTP, the direct interaction between F-subcomplex and ARF1-GTP reduces the oscillation between the two subcomplexes, thereby driving the membrane-bound coatomer to a more stabilized (less oscillation) form.  This stabilized coatomer is then able to assemble into oligomers, which together with ARF1, drives COPI vesicle formation.