[SCAN] The role of asymmetric PTMs on the behavior of protein homodimers and oligomers

Title: The role of asymmetric post-translational modifications on the behavior of protein homodimers and oligomers

Speaker: Federico Herrera

Abstract: The post-translational modifications (PTMs) of proteins are two major currencies in cell signaling. They control the activity and behavior of many proteins and eventually the function and fate of cells, tissues and organisms. PTMs are also very interesting targets for therapeutics, as they are most often transient and performed by enzymes. Kinases, phosphatases, acetylases or deacetylases are part of what is known as the “druggable genome”. Most basic PTM research focuses on 1) identifying key, rate-limiting PTMs that turn on or off a particular protein function or behavior; or 2) associating a particular rate-limiting PTM with a biological consequence. In these studies, there is an implicit assumption: that all target proteins are equally and simultaneously modified, and therefore the whole population of molecules goes from an ON state to an OFF state (or viceversa). Although it is certainly true that the proportion of proteins that are modified may be enough to carry out a particular function, what is this proportion? The disease-related proteins Huntingtin (an intrinsically disordered protein) and STAT3 (a transcription factor) have more than 80 PTMs identified. Do you think probable that the whole pool of these proteins will have exactly the same OFF PTM pattern in resting state? Or change it to ON in an All-or-Nothing manner when the stimulus triggers their pathways? If the pools are heterogeneous, what would be the consequences? And if they are not, how is such homogeneity possible? These questions have no answer, and I am not giving you one this Wednesday. I will only tell you a story of how I got to these questions.

ITQB NOVA Virtual Auditorium
https://zoom.us/j/93139069443