D6: Structural Biology and Biophysics I – 22827 (Fall 2024)
D7: Structural Biology and Biophysics II – 24284 (Spring 2024)
(2 hrs/week; 1 CP)
Stephan Grzesiek, Sebastian Hiller, Rod Lim, Timm Maier
The Structural Biology and Biophysics Seminar series (SBBS) is organized by PhD students of the Biozentrum, University of Basel since 2009. World-leading scientists are invited to present their current work to an audience of students, researchers and PIs. Typical lectures in this series describe applications of advanced structural biology and biophysics methods to solve biological problems. Methods include NMR spectroscopy, X-ray crystallography, cryo-electron microscopy, surface plasmon resonance and atomic force microscopy, but not only. The list of the past SBBS speakers is accessible here.
The talks take place on Tuesdays, the time will depend on speaker, room U1.197
Unless mentioned, attendance is open to all interested people, without registration. The spring semester 2024 is the following:
February 27, 2024 at 12:15
SBBS introductory meeting for students
ZOOM - link TBA on the day
March 19, 2024 at 12:15, room U1.197
Title: Conformational ensembles of the human intrinsically disordered proteome
Intrinsically disordered proteins and regions (collectively IDRs) are pervasive across proteomes in all kingdoms of life, help shape biological functions, and are involved in numerous diseases. IDRs populate a diverse set of transiently formed structures yet defy commonly held sequence-structure-function relationships. Recent developments in protein structure prediction have led to the ability to predict the three-dimensional structures of folded proteins at the proteome scale and have enabled large-scale studies of structure-function relationships. In contrast, knowledge of the conformational properties of IDRs is scarce, in part because the sequences of disordered proteins are poorly conserved and because only few have been characterized experimentally. In my talk I will describe how we can use molecular simulations with coarse- grained models to study the relationship between sequence, conformational properties, and functions of IDRs.
First, I will describe how we have used experimental data on more than 50 different proteins to learn a coarse-grained molecular energy function to predict conformational properties of IDPs. By globally optimizing a transferable model, called CALVADOS, we can study the conformational ensemble of an IDP in the absence of experimental data. I will describe the Bayesian formalism we developed to parameterize CALVADOS by targeting experimental data on IDRs. I will briefly describe how this model enables us to study interactions within and between IDRs in biomolecular condensates.
Second, I will describe how CALVADOS makes it possible to perform large-scale simulations to explore the relationship between sequence, structure, and function of IDRs. I will describe how we have generated conformational ensembles of all intrinsically disordered regions of the human proteome, and used these to provide insight into sequence-ensemble relationships and evolutionary conservation of IDR properties.
Finally, I will describe initial work on how we can use the information encoded in CALVADOS to design disordered proteins with desired conformational properties. I will describe the basic design algorithm and experimental validation on both single-chain compaction and measurements of phase separation.
Prof. Kresten Lindorff-Larsen
March 26, 2023 at 12:15, room U1.197
Title: Structural basis for bacterial protein disaggregation and proteolysis
Protein homeostasis is meticulously maintained across all cells, spanning from archaea to humans. Any deviation from the equilibrium of the proteome, induced by stress or cellular aging, leads to the accumulation of misfolded proteins, contributing to cellular toxicity. A complex proteostasis network actively manages misfolded proteins through processes such as refolding, degradation, or sequestration into intracellular inclusions. Integral to this protein quality control system are ATPases from the AAA+ superfamily (ATPases Associated to a variety of cellular Activities).
These AAA+ proteins, universally present in organisms, share a common structural fold for ATP hydrolysis, but each possesses distinct function-specific domains, enabling specialization in particular cellular activities and interactions with regulatory protein partners.
Our work focuses on the structural investigation of bacterial Hsp100 AAA+ chaperones involved in protein quality control. We aim at understanding their fine-tuned regulation, which is absolutely required by the bacterium to survive harsh environment conditions and useful for us in the effort of killing pathogenic bacterial strains. Using cryo-EM in combination with biochemical functional assays, we can describe the molecular tuning mechanisms used by bacteria to assure the disaggregation or proteolysis of toxic protein species only, while leaving intact functional protein molecules.
April 16, 2024 at 12:15, room U1.197
Title: Distinct roles of adaptor proteins in COP1 ubiquitination and transcriptional control
Important information for students enrolled at the University of Basel:
- You can earn one credit point (CP) by registering to the course.
- To get the CP for this course, all of the proposed seminars have to be attended from start to finish and a written exam in the form of an essay must be passed.
- It is your responsibility to check this website for eventual updates/changes to the program.
- Each in-person seminar is followed by a lunch with the speaker. Contact the host if you are interested in participating.