Thesis defense Gabrielle van Tilburg

On March 14th, 2023 15.00 Gabrielle van Tilburg will defend her thesis ‘Exploring the nature of ubiquitin linkage-specific binding; From Ubiquitin binding domains to full-length proteins' in the Groot Auditorium, Academiegebouw.

Promotor: Prof. Dr. J. J. Neefjes

Co-promotor: Dr. G. J. van der Heden van Noort

Thesis defense Gabrielle van Tilburg


In the elaborate world of proteins, ubiquitin is only a tiny protein; counting no more than 76 amino acids. Despite its small size however, it can regulate a wide range of cellular processes. Part of this ability to influence so many processes comes from its capacity to form ubiquitin polymers through 8 internal, different conjugation sites. Several proteins can recognize one or a few of the polyubiquitin variants that result from this selfconjugation: a phenomenon called linkage-specific binding. As can be imagined, a complex world originates from the plethora of possible polyubiquitin variants; one that is still not fully understood due to lack of proper tools. This thesis describes an effort to create a landscape of ubiquitin linkage-specific binding through various approaches. The journey starts from small, isolated ubiquitin binding domains and proceeds to finding linkage specific ubiquitin binding proteins using non-hydrolyzable ‘click’ diubiquitin proteins as bait. This leads to characterization of the functional consequences of one of the major hits found: K27Ub2 binding to the deubiquitinase UCHL3.Ubiquitin linkage-specificity and the recognition thereof is an important concept in the tight regulation of cellular activity. 


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