Project Details
Projekt
GRK 1026: Conformational Transitions in Macromolecular Interactions
Subject Area
Basic Research in Biology and Medicine
Term
from 2005 to 2013
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 373608
The Anfinsen concept, that the one-dimensional primary polypeptide sequence holds the key to the three dimensional structure and thereby activity of a protein, is a fundamental tenet of modern biochemistry. The translation of the DNA-encoded sequence into a correctly folded polypeptide chain is essential for the vitality of the cell. Over the past decade, molecular chaperones and other enzymes have been identified that uphold this crucial activity. Even a partial breakdown in the control of protein folding can have disastrous effects, as witnessed by the debilitating neurodegenerative disorders, Morbus Alzheimer and Creutzfeld-Jakob disease.
Yet there is an increasing body of evidence that the primary structure in itself is insufficient to define the precise three dimensional arrangement of the resulting protein product. This is because the thermodynamic energy profile of a folded protein exhibits a number of possible minima, with low energetic barriers between them. Nature has allowed some polypeptide sequences to adopt alternative folding patterns, resulting in differing functional species. This is particularly important if the function of a single polypeptide requires a response to changing molecular environments. Such dynamic responses have been observed upon protein interactions with representatives of the three major biological macromolecular classes: lipid membranes, nucleic acids and proteins.
The goal of Research Training Group is to understand the relationship between folding transitions and biological action. Protein folding from the denatured state, both in vitro and enzymatically controlled, is a focal point in Halle. Building on this expertise, eleven scientists have decided to join forces to investigate the roles of folding transitions in macromolecular interactions. Making up ten groups from the departments of biochemistry/biotechnology, biology, chemistry and physics, as well as the Max-Planck-Forschungsstelle für Enzymologie der Proteinfaltung, we seek to examine the effects of such transitions on protein-lipid, protein-nucleic acid and protein-protein interactions at a biophysical, biochemical and cell biological level, under the integrative auspices of a Research Training Group.
Yet there is an increasing body of evidence that the primary structure in itself is insufficient to define the precise three dimensional arrangement of the resulting protein product. This is because the thermodynamic energy profile of a folded protein exhibits a number of possible minima, with low energetic barriers between them. Nature has allowed some polypeptide sequences to adopt alternative folding patterns, resulting in differing functional species. This is particularly important if the function of a single polypeptide requires a response to changing molecular environments. Such dynamic responses have been observed upon protein interactions with representatives of the three major biological macromolecular classes: lipid membranes, nucleic acids and proteins.
The goal of Research Training Group is to understand the relationship between folding transitions and biological action. Protein folding from the denatured state, both in vitro and enzymatically controlled, is a focal point in Halle. Building on this expertise, eleven scientists have decided to join forces to investigate the roles of folding transitions in macromolecular interactions. Making up ten groups from the departments of biochemistry/biotechnology, biology, chemistry and physics, as well as the Max-Planck-Forschungsstelle für Enzymologie der Proteinfaltung, we seek to examine the effects of such transitions on protein-lipid, protein-nucleic acid and protein-protein interactions at a biophysical, biochemical and cell biological level, under the integrative auspices of a Research Training Group.
DFG Programme
Research Training Groups
Applicant Institution
Martin-Luther-Universität Halle-Wittenberg
Participating Institution
Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. (MPG)
Spokesperson
Professor Dr. Milton T. Stubbs
Participating Researchers
Professor Dr. Steffen Abel; Professorin Dr. Kirsten Bacia; Professor Dr. Jochen Balbach; Professor Dr. Alfred Blume; Professorin Dr. Karin D. Breunig; Privatdozent Dr. Ralph Golbik; Dr. Andreas Kerth; Privatdozent Dr. Hauke Lilie; Privatdozentin Dr. Annette Meister; Professor Dr. Gary Sawers; Dr. Cordelia Schiene-Fischer; Professorin Dr. Elisabeth Schwarz; Professorin Dr. Andrea Sinz
