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Beckmann Lab - Research

Membrane Protein Targeting and Translocation

Lipid-based membranes form boundaries for all cells and ensure their internal compartmentalization, thus being a key element in all living organisms. Unique membrane-associated processes, such as selective molecular transport, energy conversion or sensing and transduction of environmental signals are carried out by thousands of dedicated proteins embedded into or anchored at the membrane surface. When being non-functional or de-regulated, membrane proteins often lead to perturbations in cellular homeostasis and development of pathologies in humans that makes them a major target for pharmacological treatment.

The three-dimensional structure, or the fold, of a membrane protein is a major determinant of its functional state, but currently we have a limited understanding of the process of protein folding in the biological membrane. The process starts at the ribosome translating a nascent membrane protein by the appearance of a signal sequence. Already now the growing chain is recognized by the signal recognition particle (SRP) that delivers the translating ribosome to a membrane-embedded Sec translocon that serves as a protein-conducting channel. The Sec translocon is a conserved cellular machine that facilitates membrane protein insertion and also passage of hydrophilic polypeptide chains though the membrane. With ongoing translation, the translocon “reads out” the physico-chemical properties of the nascent peptide and either inserts the membrane-targeted hydrophobic domains or transports more polar regions across the membrane, thus helps to establish the genetically encoded topology of the newly built protein.

Aiming for a comprehensive understanding of the membrane protein biogenesis we use cryo-EM in combination with biochemical and biophysical analysis. By studying functional complexes of the ribosome with its molecular partners, such as SRP, the translocon and accessory proteins, the lab has been able to reconstruct important parts of the multi-stage pathway of the membrane protein targeting, insertion and folding.