@article{LilieBaerKettneretal.2011,
  author    = {Lilie, Hauke and B{\"a}r, Dorit and Kettner, Karina and Weininger, Ulrich and Balbach, Jochen and Naumann, Manfred and M{\"u}ller, Eva-Christina and Otto, Albrecht and Gast, Klaus and Golbik, Ralph},
  title     = {Yeast hexokinase isoenzyme ScHxk2 : stability of a two-domain protein with discontinuous domains},
  issn      = {0269-2139},
  year      = {2011},
  abstract  = {The hexokinase isoenzyme 2 of Saccharomyces cerevisiae (ScHxk2) represents an archetype of a two-domain protein with the active site located in a cleft between the two domains. Binding of the substrate glucose results in a rigid body movement of the two domains leading to a cleft closure of the active site. Both domains of this enzyme are composed of discontinuous peptide sequences. This structural feature is reflected in the stability and folding of the ScHxk2 protein. Structural transitions induced by urea treatment resulted in the population of a thermodynamically stable folding intermediate, which, however, does not correspond to a molecule with one domain folded and the other unfolded. As demonstrated by different spectroscopic techniques, both domains are structurally affected by the partial denaturation. The intermediate possesses only 40\% of the native secondary structural content and a substantial increase in the Stokes radius as judged by circular dichroism and dynamic light scattering analyses. One-dimensional 1H NMR data prove that all tryptophan residues are in a non-native environment in the intermediate, indicating substantial changes in the tertiary structure. Still, the intermediate possesses quite a high stability for a transition intermediate of about ;G = ;22 kJ mol;1.},
  language  = {en}
}
@article{LilieBaerKettneretal.2011,
  author    = {Lilie, Hauke and Baer, Dorit and Kettner, Karina and Weininger, Ulrich and Balbach, Jochen and Naumann, Manfred and Mueller, Eva-Christina and Otto, Albrecht and Gast, Klaus and Golbik, Ralph and Kriegel, Thomas},
  title     = {Yeast hexokinase isoenzyme ScHxk2 stability of a two-domain protein with discontinuous domains},
  series = {Protein engineering design \& selection},
  volume    = {24},
  journal   = {Protein engineering design \& selection},
  number    = {1-2},
  publisher = {Oxford Univ. Press},
  address   = {Oxford},
  issn      = {1741-0126},
  doi       = {10.1093/protein/gzq098},
  pages     = {79 -- 87},
  year      = {2011},
  abstract  = {The hexokinase isoenzyme 2 of Saccharomyces cerevisiae (ScHxk2) represents an archetype of a two-domain protein with the active site located in a cleft between the two domains. Binding of the substrate glucose results in a rigid body movement of the two domains leading to a cleft closure of the active site. Both domains of this enzyme are composed of discontinuous peptide sequences. This structural feature is reflected in the stability and folding of the ScHxk2 protein. Structural transitions induced by urea treatment resulted in the population of a thermodynamically stable folding intermediate, which, however, does not correspond to a molecule with one domain folded and the other unfolded. As demonstrated by different spectroscopic techniques, both domains are structurally affected by the partial denaturation. The intermediate possesses only 40\% of the native secondary structural content and a substantial increase in the Stokes radius as judged by circular dichroism and dynamic light scattering analyses. One-dimensional H-1 NMR data prove that all tryptophan residues are in a non-native environment in the intermediate, indicating substantial changes in the tertiary structure. Still, the intermediate possesses quite a high stability for a transition intermediate of about Delta G = -22 kJ mol(-1).},
  language  = {en}
}
@article{DieterichLindemannMoskoppetal.2022,
  author    = {Dieterich, Peter and Lindemann, Otto and Moskopp, Mats Leif and Tauzin, Sebastien and Huttenlocher, Anna and Klages, Rainer and Chechkin, Aleksei V. and Schwab, Albrecht},
  title     = {Anomalous diffusion and asymmetric tempering memory in neutrophil chemotaxis},
  series = {PLoS Computational Biology : a new community journal},
  volume    = {18},
  journal   = {PLoS Computational Biology : a new community journal},
  number    = {5},
  publisher = {PLoS},
  address   = {San Fransisco},
  issn      = {1553-734X},
  doi       = {10.1371/journal.pcbi.1010089},
  pages     = {26},
  year      = {2022},
  abstract  = {Neutrophil granulocytes are essential for the first host defense. After leaving the blood circulation they migrate efficiently towards sites of inflammation. They are guided by chemoattractants released from cells within the inflammatory foci. On a cellular level, directional migration is a consequence of cellular front-rear asymmetry which is induced by the concentration gradient of the chemoattractants. The generation and maintenance of this asymmetry, however, is not yet fully understood. Here we analyzed the paths of chemotacting neutrophils with different stochastic models to gain further insight into the underlying mechanisms. Wildtype chemotacting neutrophils show an anomalous superdiffusive behavior. CXCR2 blockade and TRPC6-knockout cause the tempering of temporal correlations and a reduction of chemotaxis. Importantly, such tempering is found both in vitro and in vivo. These findings indicate that the maintenance of anomalous dynamics is crucial for chemotactic behavior and the search efficiency of neutrophils. The motility of neutrophils and their ability to sense and to react to chemoattractants in their environment are of central importance for the innate immunity. Neutrophils are guided towards sites of inflammation following the activation of G-protein coupled chemoattractant receptors such as CXCR2 whose signaling strongly depends on the activity of Ca2+ permeable TRPC6 channels. It is the aim of this study to analyze data sets obtained in vitro (murine neutrophils) and in vivo (zebrafish neutrophils) with a stochastic mathematical model to gain deeper insight into the underlying mechanisms. The model is based on the analysis of trajectories of individual neutrophils. Bayesian data analysis, including the covariances of positions for fractional Brownian motion as well as for exponentially and power-law tempered model variants, allows the estimation of parameters and model selection. Our model-based analysis reveals that wildtype neutrophils show pure superdiffusive fractional Brownian motion. This so-called anomalous dynamics is characterized by temporal long-range correlations for the movement into the direction of the chemotactic CXCL1 gradient. Pure superdiffusion is absent vertically to this gradient. This points to an asymmetric 'memory' of the migratory machinery, which is found both in vitro and in vivo. CXCR2 blockade and TRPC6-knockout cause tempering of temporal correlations in the chemotactic gradient. This can be interpreted as a progressive loss of memory, which leads to a marked reduction of chemotaxis and search efficiency of neutrophils. In summary, our findings indicate that spatially differential regulation of anomalous dynamics appears to play a central role in guiding efficient chemotactic behavior.},
  language  = {en}
}