Paavilainen Lab


Protein homeostasis refers to regulation of functionality of all individual proteins of the proteome. Proteins prone to misfolding present a particular challenge to the homeostasis machinery whose modulation by small molecules has been proven to provide therapeutic benefits for multiple diseases. Many of these small molecules are derived from complex natural products, and understanding their mechanisms of action can help unravel the complex functions of different homeostasis regulators.

In eukaryotes, the co-translational translocation pathway is necessary for the functional expression of most secretory and membrane proteins. We aim at defining molecular functions of cellular factors that influence regulation of protein homeostasis at the level of co-translational translocation to the endoplasmic reticulum as well as investigating the mechanisms by which specific small-molecules perturb this process. Ultimately we aim to discover novel protein homeostasis regulators whose inhibition could be used for therapeutic advantage.

Fig1. Artistic view of our current understandings of protein translocation across ER in a eukaryotic cells. Nearly one third of celluar proteins are sorted on ER membrane through cooradinated function of ribosomes-SRP-SR and Sec61 translocon. In many cases additional cofactors assist Sec61 translocon through an unknown mechanism. Small molecule translocation inhibitors provide the mechanistic view of protein translocation intermediate.