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Momentum Protein Interaction Group:

Group leader:

Attila Reményi, associate research professor, group leader 

Group members:

Anita Alexa, research fellow

György Kardos, research fellow

Bartis Domokos, research fellow

Gábor Glatz, research fellow

András Zeke, research fellow

Marianna Rakács, lab assistant

Pongorné Klára Kirsch, PhD student

Péter Sok, PhD student

Ádám Levente Póti, PhD student

Gergő Gógl, PhD student

Signaling complexes: structure, function and drug design

We use the human mitogen activated protein kinase (MAPK) network as a model system to discover how intracellular signaling networks are built. Work in the lab involves three-dimensional structure solution by X-ray crystallography, SAXS and NMR. We develop assays for studying protein-protein interactions and protein kinase activity in vitro as well as in cells.  We also apply a systems biology centered approach to discover important regulatory connections underlying inflammation and cancer.

  

 

 

The portrait of a molecular switch involved in promoting cellular growth. The figure shows the crystal structure of the ERK2-RSK1 protein kinase complex (ERK2 in orange and RSK1 in gray). The yellow segment in the gray molecule works as a molecular switch, if it is modified by the orange molecule then the former gets turned on, and this ultimately will promote growth in cells.

Publications:

https://vm.mtmt.hu//search/slist.php?nwi=1&inited=1&ty_on=1&url_on=1&cite_type=2&orderby=3D1a&lang=1&location=mtmt&stn=1&AuthorID=10013627

5 selected publications (2010-2015):

Garai Á, Zeke A, Gógl G, Töro I, Fördos F, Blankenburg H, Bárkai T, Varga J, Alexa A, Emig D, Albrecht M, Reményi A (2012) Specificity of linear motifs that bind to a common mitogen-activated protein kinase docking groove. SCIENCE SIGNALING 5: ra74

Glatz G, Gogl G, Alexa A, Reményi A (2013) Structural Mechanism for the Specific Assembly and Activation of the Extracellular Signal Regulated Kinase 5 (ERK5) Module. JOURNAL OF BIOLOGICAL CHEMISTRY 288, 8596-8609

Gógl G, Schneider KD, Yeh BJ, Alam N, Nguyen AN, Moses AM, Hetényi C, Reményi A*, Weiss EL* (2015) The structure of an NDR/LATS kinase – mob complex reveals a novel kinase-coactivator system and substrate docking mechanism. PLOS BIOLOGY 13, e1002146

Alexa A, Gogl G, Glatz G, Garai A, Zeke A, Varga J, Dudas E, Jeszenoi N, Bodor A, Hetenyi C, Reményi A (2015) Structural assembly of the signaling competent ERK2-RSK1 heterodimeric protein kinase complex. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 112, 2711-2716

Zeke A, Bastys T, Alexa A, Garai A, Meszaros B, Kirsch K, Dosztanyi Z, Kalinina OV, Reményi A (2015) Systematic discovery of linear binding motifs targeting an ancient protein interaction surface on MAP kinases. MOLECULAR SYSTEMS BIOLOGY 11, 837

 

International collaborations:

 Eric L. Weiss – Northwestern University, USA

Marie Bogoyevitch – University of Melbourne, Ausztrália

Krishna Rajalingam – Johannes Gutenberg-Universität Mainz, Németország

EU-OPENSCREEN: http://www.eu-openscreen.eu/