Role of two helper proteins
In experiments with bacterial proteins, the researchers were able to clarify the role of two helper proteins – an insertase and a translocase – that enable the membrane proteins to embed themselves in the membrane. Insertase is a single protein, while translocase is a complex composed of multiple proteins. Both of them ensure that a pore opens up in the membrane. “In the case of insertase, we can think of this pore as a slide. The membrane protein is initially present as an unstructured peptide strand that slips down this slide into the membrane. In the membrane, this peptide strand then takes on its functional three-dimensional shape,” explains ETH Professor Müller. “Once the membrane protein has successfully become three-dimensional and embedded itself in the membrane, the helper protein detaches and forms a slide at a different location in the membrane for the next protein,” he continues.
Up to now, research into how these helper proteins function was imprecise and used only short peptides or was conducted only outside of biomembranes. “We have now observed and described for the first time, step by step, how an entire protein embeds itself in a membrane and takes on a three-dimensional form,” says Tetiana Serdiuk, a postdoc in ETH Professor Müller’s group and the study’s first author.
The ETH researchers were also able to show the differences in how insertases and translocases work: insertases insert peptide strands into the membrane relatively quickly but clumsily. “This means they work well particularly with small proteins,” says Müller. Translocases, on the other hand, insert peptide strands into the membrane section by section, making them better suited for more complex proteins.