|Project Leader:||Birte Hernandez Alvarez|
|Department:||Protein Evolution - Lupas|
|Phone:||+49 7071 601-340|
|Fax:||+49 7071 601-349|
|Staff:||Alphabetical List | Alumni|
In our group we use various biochemical, biophysical and microbiological techniques to explore the structural characteristics of proteins and their impact on protein function. As many eukaryotic proteins and protein domains have prokaryotic counterparts, we utilize bacteria as model systems. Single-cell systems and their clear protein domain composition simplify the functional analysis of proteins and the elucidation of their evolutionary conservation. That way we are able to draw conclusions that are unreachable at a eukaryotic level.
One of our projects involves research on cereblon, a protein that is known to cause developmental defects in humans in response to drugs such as thalidomide and its derivatives. Although most likely involved in the regulation of numerous cell responses, cereblon substrate recognition has yet to be understood, despite the fact that its thalidomide-binding domain (CULT) is well studied and highly conserved from bacteria to man. Using a bacterial representative, we are now exploring the range of compound classes that are able to bind to the cereblon CULT domain [1, 2].
More recently we identified a family of homotrimeric cell envelope proteins from prokaryotes, which we refer to as membrane-attached proteins of prokaryotes and mitochondria, containing a coiled-coil stalk (mempromCC). The only functionally characterized members of the family so far are the eukaryotic homologs from human and yeast, which seem to be crucial for the assembly of distinct mitochondrial membrane proteins. Our research will focus on achieving structural and functional insight into mempromCC proteins by using prokaryotic model organisms.
 Hartmann MD., Boichenko I., Coles M., Zanini F., Lupas AN., Alvarez BH. (2014) Thalidomide mimics uridine binding to an aromatic cage in cereblon. J Struct Biol 188(3):225-32
 Hartmann MD., Boichenko I., Coles M., Lupas AN., Alvarez BH. (2015) Structural dynamics of the cereblon ligand binding domain. PLoS One 10(5):e0128342