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The aim of the project entitled “Approach to structures of difficult protein targets using new mass spectrometry-based methods“, granted in 2015 by the Polish Ministry of Science (MAESTRO 2014/14/A/NZ1/00306), was structural characterization of biologically important protein assemblies selected from a class of protein systems difficult in structural studies, for which classic methods are not applicable or fail. For this aim new, alternative methods, mainly based on mass spectrometry (MS) were proposed, giving hope to overcome many difficulties accompanying the structural studies of such systems. These methods may help to break the gridlock accompanying the studies of important, sometimes basic biological structures caused by the inadequacy of classic methods of structure analysis, like X-ray, NMR or cryo-EM. Specifically, project was subdivided into four tasks specifying classes of targets of interest: (1) intermediate filament proteins with their interactors, (2) kinetochore and centriole subcomplexes, (3) histone pre-mRNA cleavage complex, (4) Ab peptide oligomers, involved in Alzheimer’s disease, (5) membrane proteins (RAGE receptor, bacterial toxins). These targets represent selected general cellular processes, often involved in major human pathologies. Their structural analysis, important for design of therapeutically beneficial modifiers was often hampered by lack of appropriate analytical tools.

Vimentin ULF
Vimentin ULF, obtained by fitting 8 vimentin tetramers into cryo-EM density (manuscript in preparation)