Dr. Roman Fudim
|
|
Room: 401 Email: fudimrox@hu-berlin.de Tel: (030) 2093 8686 |
The scope of my project is the mechanism underlying the bistability of the so-called non-visual opsins. Opsins are a group of transmembrane photoreceptor proteins which cover all domains of life. What they all have in common is the chromophore Retinal which is covalently linked to a Lysin residue in their seventh transmembrane helix. Under a light pulse of a certain wavelength the protein undergoes a conformational change which elicits some sort of downstream signal, i.e. G-Protein signaling, Ion-flux et cetera. Usually the chromophore is than hydrolyzed and has to be recovered by a certain isomerase, or the protein recovers into the initial dark state by undergoing a certain photocycle.
The opsins I work with behave differently. They have two stable states and can be switched from one to another with light of a certain wavelength - what makes them “molecular switches” with an “on” and “off” configuration. These proteins play an important role in various organisms, e.g. controlling circadian clock, G-protein coupled signaling. However, their molecular functioning still lacks understanding.
Therefore, my aim is to study different kinds of bistable opsins and characterize them spectroscopically using UV/Vis, Transient Absorption, IR and Raman spectroscopy. Another important part is to investigate the structural architecture which allows the protein to work as it does. The first step is to establish a system for heterologous expression with a high-protein yield. Therefore, I am working with different kinds of cell systems. This project is in close collaboration with Ulrike Scheib who will investigate the downstream signaling of bistable variants.
Publications
Scheib, U., Stehfest, K., Gee, C. E., Körschen, H.G., Fudim, R., Oertner, T. G., and Hegemann, P. (2015) The rhodopsin-guanylyl cyclase of the aquatic fungus Blastocladiella emersonii enables fast optical control of cGMP signaling. Science Signaling http://www.oertner.com/PDF/Scheib2015.pdf
Fudim R, Mehlhorn J, Berthold T, Weber S, Schleicher E, Kennis JT, Mathes T. (2015) Photoinduced formation of flavin radicals in BLUF domains lacking the central glutamine. FEBS J. 2015 Aug;282(16):3161-74. doi: 10.1111/febs.13297. Epub 2015 May 6.
Luck M, Mathes T, Bruun S, Fudim R, Hagedorn R, Tran Nguyen TM, Kateriya S, Kennis JT, Hildebrandt P, Hegemann P. A photochromic histidine kinase rhodopsin (HKR1) that is bimodally switched by ultraviolet and blue light. J Biol Chem. 2012 Nov 16;287(47):40083-90. doi: 10.1074/jbc.M112.401604. Epub 2012 Oct 1. PubMed PMID: 23027869; PubMed Central PMCID: PMC3501036.
http://www.jbc.org/content/287/47/40083.full.pdf+html
Yizhar O, Fenno LE, Prigge M, Schneider F, Davidson TJ, O'Shea DJ, Sohal VS, Goshen I, Finkelstein J, Paz JT, Stehfest K, Fudim R, Ramakrishnan C, Huguenard JR, Hegemann P, Deisseroth K. Neocortical excitation/inhibition balance in information processing and social dysfunction. Nature. 2011 Jul 27;477(7363):171-8. doi: 10.1038/nature10360. PubMed PMID: 21796121.
http://www.nature.com/nature/journal/vaop/ncurrent/full/nature10360.html