Protein folding and complex assembly are crucial processes for cell survival. Molecular chaperones accomplish these tasks by recognizing folding intermediates and by prevention of protein aggregation. Our work is aimed at the structure and function of molecular chaperones and associated proteins, using X-ray crystallography as core technique.
The focus of our group is the structure and function of nucleotide exchange factors (NEF) of the molecular chaperone Hsp70. During the folding reaction, Hsp70 undergoes a nucleotide-dependent conformational cycle. In the ATP state, protein substrate binding is highly dynamic while in the ADP and the nucleotide-free state, substrate is tightly bound. Co-chaperones regulate the ATPase cycle of Hsp70 either by triggering of ATP hydrolysis or by efficient exchange of ADP to ATP. For the latter reaction, several classes of nucleotide exchange factors have been identified in eukaryotes. Homologs to the prokaryotic NEF GrpE are found in mitochondria and plastids. BAG domain proteins, Fes1p/HspBP1 and Hsp110 homologs are present in the cytosol and the endoplasmic reticulum (ER). In many organisms, the Hsp110 proteins are essential and appear to be the major NEFs in eukaryotes. The crystal structures of the prototypical complexes of HspBP1 and of the S. cerevisiae Hsp110 protein Sse1p with Hsp70 were solved in our group, revealing the details of their nucleotide exchange mechanisms. The structural data were backed by extensive biochemical studies.
A further interest of the group is the folding and assembly of the RuBisCO enzyme complex. The crystal structure of the assembly chaperone RbcX in complex with the C-terminal peptide of the large RuBisCO subunit revealed how RbcX specifically recognizes its substrate.
People involved in the work
Leonie Mönkemeyer, Ph.D. student