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INEKE BRAAKMAN

Unfolding Protein Folding

Ineke Braakman is professor cellular protein chemistry at the Utrecht University and member of the Board of Chemical Sciences at NWO. Her research is dedicated to understanding the mechanisms and regulation of protein folding and assembly processes in cells, with a focus on diseases that are caused by protein misfolding.

ABSTRACT
When proteins are synthesized, they will not remain unfolded; secondary and tertiary structure start to form instantaneously. Still, in cells, for most proteins it takes 30 minutes or more to fold into the native, functional state. During the full folding time, proteins may deviate from the native path, either reversibly or irreversibly via nonnative intra- and intermolecular interactions. Each cellular compartment is equipped with a large mass of molecular chaperones that work in complexes, sequentially or simultaneously, and prevent immature proteins from finding, binding, and staying with the wrong partners. We have generated a deep understanding of the folding of (membrane and soluble) multidomain proteins in live cells, using biochemical and molecular (cell) biological approaches. With this knowledge we are exploring the regulation of folding by chaperone complexes, the role of cellular stress responses in regulating chaperone action and quantity, and the interplay with environmental factors such as membrane shape and compartment size.

 

Understanding protein folding directly impacts a range of inherited and neurodegenerative diseases, where functional defects arise from misfolding, either leading to loss of function, as in cystic fibrosis, or to gain of function, as in amyloid accumulation. Small-molecule drugs that target a misfolded protein have entered the clinic without known mode of action. Whether a molecular chaperone or a small molecule, our folding studies uncover their effects on the target protein.

BIO

Affiliation

Cellular Protein Chemistry, Science4Life, Faculty of Science,

Utrecht University,

The Netherlands

Research tracks

Chemistry of Life

More information

Ineke Braakman's homepage

Keynote speaker

Wednesday 11 December

13:50 - 14:20h

NWO logo - JPG klein.jpg

CHAINS 2019 is organised by NWO Domain Science with the support of partners Holland Chemistry and KNCV