Wilbert Boelens

Foto Wilbert E-mail: w.boelens@ncmls.ru.nl
Phone: +31(0)24 3616753
Room: 6.46

The main goal of the research of Wilbert Boelens is to try to understand how cells function under stress conditions and to determine the effect of stress-induced posttranslational protein modifications. The work of his group is focused on two topics: ‘Small heat-shock proteins: structure, function and pathology’ and ‘Transglutaminase 2: The importance of connecting proteins in cells’


Small heat-shock proteins: structure, function and pathology

The cell protects itself against environmental stress by synthesizing a set of special proteins, amongst which the ‘small heat-shock proteins’ (sHSPs). sHSPs are molecular chaperones that can prevent the aggregation of stress-labile polypeptides. This way, they can help to reduce the cellular concentrations of early misfolding species in the proteotoxic aggregation pathway. By virtue of these activities sHSPs play a central role in cellular proteostasis.
The human sHSP family contains ten authentic members, termed HSPB1-10, which are assembled in homo- or hetero-oligomeric structures of various sizes that will readily dissociate upon stress. The association/dissociation of these oligomers is believed to modulate their function. Dysfunctioning of these proteins is associated with different diseases, such as Alzheimer’s disease, Alexander’s disease, multiple sclerosis, myopathies, cataracts and cancer. Despite enormous progress in the field still very little is known about how the activity of sHSPs is regulated in vivo, which client proteins they protect and whether sHSPs only prevent aggregation of proteins or also help with the refolding process.


Transglutaminase 2: The importance of connecting proteins in cells

Transglutaminase 2 (TG2) catalyzes the acyl-transfer reaction between the γ-carboxamide of a peptidylglutamine (Q, amine acceptor) and the ε-amino group of a peptidyllysine (K, amine donor), leading to protein crosslinking. While TG2 is very restrictive towards the amine acceptor glutamine residue, a wide variety of amine donors can be utilized, including the primary alkylamines putrescine, spermidine and spermine, leading to the formation of monosubstituted γ-amides. Under normal physiological conditions the intracellular enzyme is silent due to its dependence on calcium. In response to extreme stresses, elevated calcium potentiate the TG2 activity, which leads to massive intracellular protein crosslinks, generating protective proteinaceous networks that may prevent leakage of harmful cell contents from dying cells, thereby lessens inflammation and tissue damage and reduces the chance of autoimmune disease. What kind of proteinaceous network is formed and how it prevents leakage of cell content is still unclear.



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