roteins, similarly to other biomolecules, are modular and hierarchical in
nature. Various building blocks serve to construct proteins of high
structural complexity and diverse functionality. In multi-domain proteins,
for example, domains are fused to each other in different combinations to
generate different functions. Despite the justified Lego metaphor to simply
the complexity of proteins 3-dimensional structures, several fundamental
properties (such as allostery or the induced-fit mechanism) demand deviation
from the Lego metaphor as plasticity and softness is essential for function.
In my lecture, I will discuss a non-Lego protein behavior in multi-domain
proteins and due to post-translational modifications. While earlier studies
showed that a protein domain is often unaffected by fusing to another domain
or becomes more stable due to a formation of a new interface between the
tethered domains, a destabilization by tethering has been reported for
several systems. Protein destabilization due to fusion to other domains
might be linked in some cases to biological function and should be taken
into account when designing large assemblies. Post-translational
modifications (PTMs), which are ubiquitous in the cell, are often believed
to regulate protein activity by changing the protein surface and introducing
new functional groups that act as a signaling tag for binding to other
molecules. We showed that PTMs may also control a protein function by
modulating the protein biophysical characteristics. PTMs, therefore, can
enrich the repertoire of protein characteristics beyond that dictated by
their sequence and can be viewed as an economical way to introduce larger
diversity to the proteins encoded in the genome. In the lecture, the effect
of glycosylation and ubiquitination on the biophysical properties of
proteins will be discussed and the linkage between the biophysics and
function of the PTMs.