Biogenesis of membrane proteins: Surprises in vivo

All living cells utilize conserved systems responsible for membrane protein biogenesis, including the signal recognition particle (SRP) and its receptor.

The SRP system contains a membrane-bound SRP-receptor and an SRP protein-RNA complex, which recognizes nascent hydrophobic peptides in the process of translation. Whereas the SRP pathway has been elucidated mainly through a remarkable series of in vitro studies, we study major aspects of the pathway in vivo.

Our results were both surprising and unpredicted. Together, these studies support an alternative order of events in the E. coli targeting pathway. Our model predicts that (i) The SRP receptor is able to deliver ribosomes to the membrane during its own translation; (ii) mRNAs of membrane proteins might be targeted to membrane associated ribosomes, independently of translation; and (iii) the SRP functions downstream of the SRP-receptor. This hypothesis is currently being further investigated in our lab, utilizing genetics, NGS, X-ray crystallography, and biochemical approaches.

 

Biogenesis of membrane proteins: Surprises in vivo

Our model for membrane protein biogenesis
1. FtsY is targeted to the membrane co-translationally and assembles on membrane lipids and/or on an unknown integral membrane protein (indicated by a question mark in the figure). After targeting, the ribosome or its large ribosomal subunit remains membrane-bound. 2. The membrane protein-encoding mRNA is targeted to membrane-bound ribosomes, forming a new translation initiation complex. 3. The emerging nascent hydrophobic polypeptide is recognized by SRP. The SRP binds the polypeptide, the ribosome and the SRP receptor, and the translating ribosome is then transferred to a membrane protein-insertion machinery (Bibi, 2011;2012).