A Biomolecular And Conformational Investigation Of Protein Ub Conjugation Processes Driven By RING-Domain Ub Transfer Enzymes

<p>Cells face and react to their environment to ensure viability or to fulfil specialized tasks. Therefore they evolved highly coordinated interconnected signalling networks to sense extra- or intra-cellular stimuli and generate diverse changes in the cellular physiology ranging from transcription modification to the activation or repression of various protein functions. These signalling networks often include molecules that can be covalently attached to other molecules such as proteins nucleic acids or lipids to alter their affinities towards binding partners. Alternatively such attachments may modulate the enzymatic activity of the modified proteins or affect their cellular localization. These attachments commonly referred as post-translational modifications (PTMs) generate quicker responses and initiate instant downstream signalling compared to the transcription/translation machinery (Walsh and Jefferis 2006). PTMs usually involve reversible covalent attachment of molecules such as phosphate methyl or acetyl groups to proteins (Cohen 2001; Walsh and Jefferis 2006; Yang and Seto 2008). Additionally proteins in eukaryotes may get modified by covalent attachment of small proteins like ubiquitin (Ub) SUMO (Small ubiquitin-related modifier) or Nedd8. These modifications are often classified as UbLyations and the modifiers as UbLs (Ubiquitin Like proteins) as Ub was the first one to be identified and characterized amongst these. In fact the attachment of Ub has been established to play many cellular roles as it can alter the function as well as the fate of the substrate proteins.</p>