The Thirup group is part of The Center for Structural Biology, MBG, AU, and has many years of experience in X-ray crystallography.
We seek to establish detailed knowledge of the three dimensional structures of the Sortilins in order to explain their differential ligand affinity and functional details.
A large number of ligands have been identified for sortilin and most of them compete for the same or overlapping binding sites. Some of the ligands e.g. neurotensin , CNTF, proGranulin, share a C-terminal hydrophobic residue which is recognized by sortilin. Other ligands, e.g proneurotrophins, sortilins propeptide, must be recognized differently and we seek to describe this recognition mode. Structure determination of complexes with adaptor proteins and their target motifs in the tails of the Sortilin and sorLA are ongoing.
Our goal is to eventually determine the structures of the ectodomains of all sortilins alone and in complex with ligands. So far we have determined the structure of the ectodomain of sortilin in complex with neurotensin and small molecule ligands. Also, we have examined the structural determinants for recognition of the sortilin and sorLA cytosolic tails by the adaptor protein GGA1.
In addition to our structural studies of the sortilins we are also studying the prokaryotic translation factors EF-Tu and EF-TS and Lysm-domain containing proteins.
The Thirup group currently has projects available for Master and PhD students. Please contact Group Leader Søren Skou Thirup directly, if interested.