Paavilainen Lab

Research

1. Cellular factors mediating biogenesis of specific secreted or membrane proteins

We are using cellular profiling experiments coupled with detailed biochemical studies to probe the roles of several conserved translocon components. This work aims at identifying new targets for altering the protein homeostasis balance for therapeutic purposes.

 

2. Mechanisms of action of small molecule natural products that specifically modulate the secretory protein biogenesis pathway.

Apratoxin Cotransin (CT7)

This aspect of our work utilizes natural product small molecules that have evolved to perturb distinct cellular events required for biogenesis of secretory and membrane proteins. We aim to dissect the mechanisms of action of these molecules and uncover their molecular targets to gain insight into the complicated process of co-translational translocation.

Recent Updates:

Mycolactone subverts immunity by selectively blocking the Sec61 translocon. Baron L, Paatero AO, Morel JD, Impens F, Guenin-Macé L, Saint-Auret S, Blanchard N, Dillmann R, Niang F, Pellegrini S, Taunton J, Paavilainen VO, Demangel C.(2016) J Exp Med. Dec 12;213(13):2885-2896.

Apratoxin Kills Cells by Direct Blockade of the Sec61 Protein Translocation Channel. Paatero AO, Kellosalo J, Dunyak BM, Almaliti J, Gestwicki JE, Gerwick WH, Taunton J, Paavilainen VO (2016) Cell Chem Biol. May 19;23(5):561-6.

3. Structural characterization of different secretory pathway components and their structural intermediates.

We use x-ray crystallography and cryo-electron microscopy to study the structures of different secretory pathway components and their conformational intermediates. We are particularly interested in understanding the substrate-selectivity in cotranslational protein translocation.

Single particle Cryo-EM structure of ribosome-bound Sec61 translocon.