Protein folding and stability at Biochemistry

Protein Folding and Stability

The research group of Carlo van Mierlo focuses on the experimental elucidation of how proteins fold, the probing of energy landscapes of protein folding (see figure), the misfolding of proteins, and the characterisation of protein folding while the nascent polypeptide emerges from the ribosome. Use is made of among others heteronuclear multi-dimensional NMR spectroscopic techniques, hydrogen/deuterium exchange methodologies, stopped-flow approaches, and of fluorescence spectroscopic techniques like (single-molecule) Förster resonance energy transfer, time-resolved anisotropy, and flavin fluorescence quenching upon cofactor binding.

Recently, in a joint effort with Jan Willem Borst and Dolf Weijers, the group embarked on the investigation of the roles of intrinsic disorder and phase separation for the plant transcription factor proteins of the AUXIN RESPONSE FACTOR (ARF) family. In many cases, phase separation originates from biomolecular interactions involving intrinsically disordered protein domains, which are in a folding state that lacks regular structural features. Such domains are predicted to be prominent for ARFs, which are crucial mediators of plant hormone response. Research involves the quantification of intrinsic disorder in the middle region of ARF proteins, the characterisation of phase separation of ARF proteins in vitro, and the determination of the generic biological relevance of ARF phase separation.