EventProf. Martin Hegner

Translation and Folding of Single Proteins in Real Time

Protein biosynthesis by the ribosome, a complex molecular machine, is inherently coupled to co-translational protein folding. How proteins fold natively with efficient fidelity while being synthesized remains largely unexplored. Understanding protein synthesis on a single-molecule level is of particular interest to the life sciences and relevant for various diseases. Although protein synthesis and folding are well-studied subjects, co-translational folding has been proven difficult to observe. Here, we follow synthesis by individual ribosomes using dual-trap optical tweezers and observe simultaneous folding of the nascent polypeptide chain in real time.

We found that co-translational folding occurs at predictable locations, exerting forces on the nascent polypeptide. Furthermore, we show that transient pauses and gradual slowing of translation occur in particular locations along the protein sequence, facilitating native secondary-structure formation. Thus, the rate of synthesis is inherently coupled to co-translational folding, assuring reliable and fast native folding.

The presentation will introduce nanomechanical measurements using optical tweezers technology in liquid environments. Then we explore the latest findings on single ribosome translation that elucidate the intricate relationship between a protein’s amino acid sequence, its co-translational nascent chain elongation rate and folding.

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Literature: Wruck, F., Katranidis, A., Nierhaus, K.H., Büldt, G., Hegner, M. (2017) Translation and folding of single proteins in real-time Proc. Natl. Acad. Sci. USA 114 (22) E4399-E4407; doi:10.1073/pnas.1617873114

About The Speaker

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Prof. Hegner studied Life Sciences at the Swiss Federal Institute of Technology, Zurich in 1984 (CH). He received his Diploma (“master of science”) degree in Cellular Biochemistry, Molecular Biology, Immunology and Toxicology in 1989 and he completed his PhD thesis in 1994 with work in the field of ‘Protein Translocation across Membranes’ and ‘Biological Scanning Probe Microscopy’ at the Swiss Federal Institute of Technology, Institute for Biochemistry in Zurich. In 1994-96 he had a post-doctoral position at the Institute of Physics in Basel in the laboratory of Prof. H.-J. Güntherodt, a pioneer in the field of scanning probe microscopy. Thereafter (’96-’99) he joined the world leading group of C. Bustamante at the Howard Hughes Medical Institute in Eugene, OR and then at University of California at Berkeley, CA as a research associate to acquire know-how in the field of single molecule manipulation with optical tweezers. In 1999 he joined the Institute of Physics at University of Basel (Switzerland) as group and project leader for biological nanoscale science within the newly founded Swiss National Centre of Competence ‘Nanoscale Science’. Until today he introduced several novel approaches to investigate molecular interactions with nanomechanical tools. In 2001 he received his ‘venia docendi’ in Experimental Physics at the University of Basel, Switzerland and in 2007 he joined the Physics faculty of the University of Dublin, Trinity College Dublin Ireland. He was appointed as Professor and pursues his interdisciplinary research in the Centre of Research on Adaptive Nanostructures and Nanodevices (CRANN) in the field of Nanobiotechnology.