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Discovering methylhistidines in human proteins

Background

Over the past 20 years, post-translational methylation of lysine and arginine residues has been firmly established as an important mechanism for the regulation of protein function and signaling in a multitude of cellular processes. The methylation of other protein residues is much less studied. Histidine can be methylated on either of the nitrogen atoms of its imidazole side chain, leading to the formation of 1-methylhistidine (1MH) or 3-methylhistidine (3MH). Both the 3MH and 1MH modifications have been observed in mammalian proteins for decades, but the methyltransferase (MTase) enzymes writing these marks have only now started to come to light. So far, only one such enzyme has been published, and that is the methyltransferase which generates 3MH in a single protein, actin.

Bildet kan inneholde: produkt, diagram, linje.

Our group specializes in the discovery of new lysine-specific MTase enzymes, but recently we have stumbled upon an exciting novel MTase that forms 1MH within histidine-rich motifs in a large number of different substrate proteins. While we observe ample histidine methylation in vitro, we must investigate whether corresponding 1MH modifications are generated in proteins in human cells and what their functional effects might be.

Master project

In this master project, you will apply fundamental molecular and cell biology techniques to discover previously uncharacterized 1MH sites in human proteins.  Through protein overexpression in human cell culture, proteomics and microscopy, you will investigate the histidine methylation status, interactions and localization of several proteins. If successful, the results of the master project will become part of a high-quality publication.

Working environment

We are a tight-knit team of scientists who enjoy working hard while having a lot of fun. You will be closely supervised by Erna Davydova (erna.davydova@ibv.uio.no) and Lisa Schroer (lisa.schroer@ibv.uio.no) in the group of P?l Falnes (pal.falnes@ibv.uio.no). Please contact one of us if you are interested.

A few relevant publications

Wilkinson, Alex W., et al. (2019). SETD3 is an actin histidine methyltransferase that prevents primary dystocia. Nature, 565(7739), 372-376.

Kernstock, S., Davydova, E., Jakobsson, M., Moen, A., Pettersen, S., M?landsmo, G. M., ... & Falnes, P. ?. (2012). Lysine methylation of VCP by a member of a novel human protein methyltransferase family. Nature communications, 3(1), 1-11.

Jakobsson, M. E., Ma?ecki, J. M., Halabelian, L., Nilges, B. S., Pinto, R., Kudithipudi, S., Munk, S., Davydova, E., Zuhairi, F. R., Arrowsmith, C. H., Jeltsch, A., Leidel, S. A., Olsen, J. V. & Falnes, P. ?. (2018). The dual methyltransferase METTL13 targets N terminus and Lys55 of eEF1A and modulates codon-specific translation rates. Nature communications, 9(1), 1-15.

Falnes, P. ?., Jakobsson, M. E., Davydova, E., Ho, A., & Ma?ecki, J. (2016). Protein lysine methylation by seven-β-strand methyltransferases. Biochemical Journal, 473(14), 1995-2009. (Review article)

 

Publisert 6. feb. 2020 14:51 - Sist endret 26. jan. 2021 11:30

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Omfang (studiepoeng)

60