Er is een eiwitrevolutie aan de gang. De ene na de andere belangrijke ontwikkeling wordt gemeld. AlphaFold, een AI-programma ontwikkeld door Googles onderzoeksafdeling DeepMind, presenteerde onlangs baanbrekend onderzoek. Hoogleraar Albert Heck: ‘Het is zeker een paradigmawisseling, maar magie is het niet.’
https://www.vprogids.nl/2021/44/editie?pagina=24
BILLERICA, Massachusetts – August 8, 2020 – Bruker Corporation (Nasdaq: BRKR) today announced a collaboration with Utrecht University to advance the study of the 3-D structures and interactions of proteins by mass spectrometry. The laboratory of Albert Heck at Utrecht University has been a leader in proteomics and the study of protein structure and interactions by mass spectrometry for over two decades. Richard Scheltema recently joined Utrecht University as group leader to focus on crosslinking mass spectrometry (XL-MS) for structural and interaction proteomics………..
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We demonstrate single-particle charge detection mass spectrometry on an Orbitrap for the analysis of megadalton biomolecular assemblies. We establish that the signal amplitudes of individual ions scale linearly with their charge, which can be used to resolve mixed ion populations, determine charge states and thus also determine the masses of individual ions. This enables the ultrasensitive analysis of heterogeneous protein assemblies including immunoglobulin oligomers, ribosomes, proteinaceous nanocontainers and genome-packed adeno-associated viruses.
Tobias P. Wörner, Joost Snijder, Antonette Bennett, Mavis Agbandje-McKenna, Alexander A. Makarov & Albert J. R. Heck
Nat Methods (2020). https://doi.org/10.1038/s41592-020-0770-7
Utrecht scientists uncover the molecular machinery in the chloroplasts of plants. This opens the way for research into protein interactions in protein complexes on the cell surface. They publish their findings in Nature Communications.
Albanese, Pascal; Tamara, Sem; Saracco, Guido; Scheltema, Richard A.; Pagliano, Cristina Nature Communications, Volume 11 (1) – Mar 13, 2020
The Barford group at @MRC_LMB revealed the structure of the kinetochore CCAN complex assembled onto a centromeric nucleosome, using our Domenico Fasci’s @UUBeta cross-linking MS data to validate assignments in the EM maps. #EPICXS #proteomics @xlinkx_pd
On March 1st, 2017 we had our festive kickoff of our three new Mass Spectrometers.
More information (in Dutch) can be found here
Professor Albert Heck has received an honory membership of the Spanish Proteomics Society. Heck was honored during the Opening Ceremony of the 6th Congress of the Spanish Proteomics Society in Cadiz on November 15th 2016.
On the picture Heck receives the award from Angel García, President of the Spanish Proteomics Society.
Researchers at Utrecht University, including Albert Heck and Simone Lemeer, have revealed structural changes in a receptor that plays a key role in many types of cancer. The changes occur before and during receptor activation. These findings provide novel clues to develop medication to target the disease. For the first time, a receptor of this size could be studied in its natural environment. The researchers are publishing their results in the journal Cell this week.
The researchers studied a receptor that can be activated by the epidermal growth factor (EGF), a hormone that stimulates cell division. Genetic defects can lead to too many of these receptors in the cell membrane. This overstimulates cell division, leading to cancer.
Natural environment
To study the EGF receptor, the Utrecht scientists used a new approach in the field of NMR spectroscopy. This enabled them to observe structural changes of the receptor in its native environment – the cell membrane. “Previously, only parts of the receptor had been analysed and then only outside its cellular environment”, says Marc Baldus, professor of NMR spectroscopy at Utrecht University and one of the publication’s authors. “We can now observe how the receptor behaves in a cellular setting. This technique has great promise and can also be used to study other proteins associated with cancer or other diseases, such as Alzheimer’s or Parkinson’s”.
Dancing around
Using the method, the researchers discovered that the receptor continually changes shape in the absence of the EGF hormone. “We believe that the receptor in its ligand free state is continually switching from a ‘closed’ to an ‘open’ position and vice-versa”, says Paul van Bergen en Henegouwen, cellular biologist at Utrecht University and one of the authors of the article. “It so to speak dances around and continuously bows for its audience”.
New cancer drugs
In his lab, Van Bergen en Henegouwen develops antibody fragments, known as nanobodies, that can specifically bind to EGF receptors. These nanobodies can therefor be used to label tumour cells, which enables the specific destruction of such cells. “Since we now know more about the structure and dynamics of the EGF receptor, we can start designing nanobodies that specifically bind to the open, active form of the receptor. This can ultimately lead to new cancer drugs.”
Publication
‘EGFR Dynamics Change during Activation in Native Membranes as Revealed by NMR’
Cell, 10 november 2016, doi.org/10.1016/j.cell.2016.10.038
Mohammed Kaplan, Siddarth Narasimhan, Cecilia de Heus, Deni Mance,Sander van Doorn, Klaartje Houben, Dusan Popov-Celeketic, Reinier Damman, Eugene A. Katrukha, Purvi Jain, Willie J.C. Geerts, Albert J.R. Heck, Gert Folkers, Lukas C. Kapitein, Simone Lemeer, Paul M.P. van Bergen en Henegouwen and Marc Baldus
This research is conducted within Utrecht University’s research theme Life Sciences and was supported by the Netherlands Organization for Scientific Research (NWO).
