Jocelyne Vreede
Coiled coil complexes
Coiled coils are widely occurring protein interaction motifs that provide a stable scaffold for various protein functions. Comprising two to seven amphipathic alpha-helices wound into a supercoil, these systems rigidify protein complexes, regulate function through binding and, surprisingly, are involved in signal transduction. In this project we use advanced molecular simulation techniques to investigate the mechanisms of the formation and functioning of three coiled-coil complexes in atomistic detail. These systems are:
1) The leucine zipper domain in the yeast transcription factor GCN4. This is the classical example of a coiled coil complex, comprising two peptide chains.
2) The HAMP domain, a linker domain in prokaryotic sensor proteins. Recently, the structure of HAMP became available, enabling a computational investigation of the unknown dynamic properties underlying signal transduction in the HAMP domain.
3) The multimerization domain of H-NS, a DNA bridging protein found in E. coli. This domain can assume two different dimeric coiled coil conformations, depending on the length of the monomers.
VENI grant 2008 (Innovational Research Incentive Scheme, NWO)
Photoactive Yellow Protein
How can a light signal, very small in size en very short in time, lead to a long-lasting, organism-wide response? To investigate (part of) this question, we study the Photoactive Yellow Protein (PYP) from the bacterium Halorhodospira halophila, where it is involved in a negative phototactile response to blue light. Comprising 125 amino acids and a covalently bound chromophore, the protein folds into a alpha-beta core capped by an N-terminal domain, containing two helices. Upon absorbing a blue-light photon as a trigger, PYP undergoes a photo cycle, starting from its receptor state. Visiting several intermediate states, the chromophore twists along its double bond to a cis configuration within picoseconds. Within microseconds of the isomerization, a proton from Glu46 (protonated in the receptor state) transfers to the chromophore, leaving a negative charge on Glu46. Driven by the new negative charge in the chromophore binding pocket, the protein subsequently unfolds to expose the chromophore and Glu46 to bulk water forming the signaling state. The completion of the photo cycle, i.e. the refolding of the protein to the receptor state pG, requires several hundreds of milliseconds. We study the conformational transitions in PYP in atomic detail, using molecular simulation methods, including parallel tempering, metadynamics and transition path sampling.
Publications
Reordering hydrogen bonds using hamiltonian replica exchange enhances sampling of conformational changes in biomolecular systems
TraR auto-inducer enhances protein backbone fluctuations in DNA binding domain
Helix formation is a dynamical bottleneck in the recovery reaction of Photoactive Yellow Protein
Predicting the signaling state of photoactive yellow protein
PAS domains: common structure, common dynamics
Predicting the reaction coordinates of millisecond light-induced conformational changes in photoactive yellow protein
CV
2009 - 2012
VENI project, University of Amsterdam
2006 - 2009
Post-doc, University of Amsterdam (Peter Bolhuis)
2005 - 2006
Post-doc, University of Amsterdam (Klaas Hellingwerf)
2001 - 2005
PhD project, University of Amsterdam (Klaas Hellingwerf, Wim Crielaard)
1996 - 2001
MSc Chemistry, University of Amsterdam (Berend Smit)