Structural and functional studies of full-length receptor tyrosine kinases

Structural and functional studies of full-length receptor tyrosine kinases

Our major research program focuses on the structural and functional studies of receptor tyrosine kinases (RTKs), a family of cell surface receptors that play a key role in regulating normal cellular processes. Defects in RTK activation are causative in many cancers and other diseases and are targeted by many drugs. To date, many crystal structures for individual domains of RTKs are available. However, structural information on full-length RTKs, either in their apo- or ligand-bound multimeric states, has been elusive because these elongated and conformationally dynamic single-pass transmembrane proteins are difficult to crystalize. Thus, the central question of how information is relayed across plasma membrane by these important proteins remains unanswered. The RTK complexes have a molecular weight ranging from 140kDa to 800kDa, which makes them suitable for cryo-EM structural determination. Our lab is currently working on several members of RTK, including EGFR, RET, IR, and IGF1R. Solving the structures of different members of the RTK family will reveal similarities and differences in the structure-function relationships within this receptor family.

Collaborators

Xuewu Zhang, Hongtao Yu, Eunhee Choi

Related Publications

Jie Li*, Eunhee Choi*†, Hongtao Yu†, Xiao-chen Bai†. Structural basis of the activation of type 1 insulin-like growth factor receptor. Nature Communications 2019;10 (1), 1-11

[DOI]

Cryo-EM analyses reveal the common mechanism and diversification in the activation of RET by different ligands
Jie Li*, Guijun Shang*, Yu-Ju Chen, Chad A Brautigam, Jen Liou, Xuewu Zhang†, Xiao-chen Bai†, eLife 2019;8: e47650.

[DOI]

Emiko Uchikawa*, Eunhee Choi†*, Guijun Shang , Hongtao Yu†, Xiao-chen Bai†. Activation mechanism of the insulin receptor revealed by cryo-EM structure of the fully liganded receptor-ligand complex. eLife 2019;8:e48630.

[DOI]