News | IMPRS for Molecules of Life

Graduation of Poo Yee Annie Yim

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Poo Yee Annie Yim

Integrative analysis and visualization of multi-omics data of mitochondria-associated diseases

RG: Bianca Habermann

Graduation of Valter Bergant

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Valter Bergant

Data-driven host-directed antiviral drug repurposing against emerging pathogens

RG: Andreas Pichlmair

Graduation of Marie-Lena Jokisch

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Marie-Lena Jokisch

Development of Genetic Code Expansion Tools to Study Post-translational Modifications

RG: Kathrin Lang

Co-first Author Publication of IMPRS-LS students Susanne Reinhardt, Isabelle Baudrexel and Philipp Steen

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Reinhardt, S.C.M.^#, Masullo, L.A.^#, Baudrexel, I.^#, Steen, P.R.^#, Kowalewski, R., Eklund, A.S., Strauss, S., Unterauer, E.M., Schlichthaerle, T., Strauss, M.T., Klein, C., and Jungmann, R.
^#equal contribution
(IMPRS-LS students are in bold)
Nature, 2023, 617, 711-716.
doi: 10.1038/s41586-023-05925-9

Ångström-resolution fluorescence microscopy

Fluorescence microscopy, with its molecular specificity, is one of the major characterization methods used in the life sciences to understand complex biological systems. Super-resolution approaches can achieve resolution in cells in the range of 15 to 20 nm, but interactions between individual biomolecules occur at length scales below 10 nm and characterization of intramolecular structure requires Ångström resolution. State-of-the-art super-resolution implementations have demonstrated spatial resolutions down to 5 nm and localization precisions of 1 nm under certain in vitro conditions. However, such resolutions do not directly translate to experiments in cells, and Ångström resolution has not been demonstrated to date. Here we introdue a DNA-barcoding method, resolution enhancement by sequential imaging (RESI), that improves the resolution of fluorescence microscopy down to the Ångström scale using off-the-shelf fluorescence microscopy hardware and reagents. By sequentially imaging sparse target subsets at moderate spatial resolutions of >15 nm, we demonstrate that single-protein resolution can be achieved for biomolecules in whole intact cells. Furthermore, we experimentally resolve the DNA backbone distance of single bases in DNA origami with Ångström resolution. We use our method in a proof-of-principle demonstration to map the molecular arrangement of the immunotherapy target CD20 in situ in untreated and drug-treated cells, which opens possibilities for assessing the molecular mechanisms of targeted immunotherapy. These observations demonstrate that, by enabling intramolecular imaging under ambient conditions in whole intact cells, RESI closes the gap between super-resolution microscopy and structural biology studies and thus delivers information key to understanding complex biological systems.

Graduation of Yevheniia Bushman

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Yevheniia Bushman

Investigation of functional and structural divergence of the Hsp16 chaperone family in Caenorhabditis elegans

RG: Johannes Buchner

Graduation of Tia Tyrsett Kuo

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Tia Tyrsett Kuo

Cryptochromes recruit to laser-induced DNA damage sites through PARP1 activity and promote repair

RG: Andreas Ladurner

Publication of IMPRS-LS student Kheewoong Baek

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Baek, K., Scott, D.C., Henneberg, L.T., King, M.T., Mann, M., and Schulman, B.A.
(IMPRS-LS students are in bold)
Cell, 2023, 186, 1895-1911.e1821.
doi: 10.1016/j.cell.2023.02.035

Systemwide disassembly and assembly of SCF ubiquitin ligase complexes

Cells respond to environmental cues by remodeling their inventories of multiprotein complexes. Cellular repertoires of SCF (SKP1-CUL1-F box protein) ubiquitin ligase complexes, which mediate much protein degradation, require CAND1 to distribute the limiting CUL1 subunit across the family of ∼70 different F box proteins. Yet, how a single factor coordinately assembles numerous distinct multiprotein complexes remains unknown. We obtained cryo-EM structures of CAND1-bound SCF complexes in multiple states and correlated mutational effects on structures, biochemistry, and cellular assays. The data suggest that CAND1 clasps idling catalytic domains of an inactive SCF, rolls around, and allosterically rocks and destabilizes the SCF. New SCF production proceeds in reverse, through SKP1-F box allosterically destabilizing CAND1. The CAND1-SCF conformational ensemble recycles CUL1 from inactive complexes, fueling mixing and matching of SCF parts for E3 activation in response to substrate availability. Our data reveal biogenesis of a predominant family of E3 ligases, and the molecular basis for systemwide multiprotein complex assembly.

Graduation of Oleksii Lyzak