Bio

Honors & Awards


  • Otto Hahn Fellow, Max Planck Society (08-01-2012)
  • Otto Hahn medal, Max Planck Society (06-15-2010)

Professional Education


  • Doctor of Philosophy, J W Goethe Universitat Frankfurt (2009)

Stanford Advisors


Publications

Journal Articles


  • K+-induced conformational changes in the trimeric betaine transporter BetP monitored by ATR-FTIR spectroscopy BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES Korkmaz, F., Ressl, S., Ziegler, C., Maentele, W. 2013; 1828 (4): 1181-1191

    Abstract

    The trimeric Na(+)-coupled betaine symporter BetP from Corynebactrium glutamicum adjusts transport activity according to the external osmolality. BetP senses the increasing internal K(+) concentration, which is an immediate consequence of osmotic upshift in C. glutamicum. It is assumed that BetP specifically binds potassium to yet unidentified binding sites, thereby inducing conformational changes resulting in activation. Atomic structures of BetP were obtained in the absence of potassium allowing only a speculative glimpse on a putative mechanism of K(+)-induced transport activation. The structural data suggest that activation in BetP is crucially linked to its trimeric state involving an interaction network between several arginines and glutamates and aspartates. Here, we describe the effect of K(+)-induced activation on the specific ionic interaction sites in terminal domains and loops and on the protomer-protomer interactions within the trimer studied by ATR-FTIR spectroscopy. We suggest that arginine and aspartate and/or glutamate residues at the trimeric interface rearrange upon K(+)-induced activation, although they remain assembled in an interaction network. Our data propose a two-step mechanism comprising first a change in solvent exposure of charged residues and second a modification of their interaction sites in a partner-switching manner. FTIR reveals a higher ?-helical content than expected from the X-ray structures that we attribute to the structurally unresolved N-terminal domain modulating regulation. In situ (1)H/(2)H exchange studies point toward an altered exposure of backbone regions to buffer solution upon activation, most likely due to conformational changes in both terminal domains, which further affects ionic interactions within the trimer.

    View details for DOI 10.1016/j.bbamem.2013.01.004

    View details for Web of Science ID 000316522100001

    View details for PubMedID 23318153

  • K(+)-induced conformational changes in the trimeric betaine transporter BetP monitored by ATR-FTIR spectroscopy. Biochim Biophys Acta. Filiz Korkmaz, Susanne Ressl, Christine Ziegler, Werner M_ntele 2013; 1828: 1181
  • Substrate specificity and ion coupling in the Na+/betaine symporter BetP EMBO JOURNAL Perez, C., Koshy, C., Ressl, S., Nicklisch, S., Kraemer, R., Ziegler, C. 2011; 30 (7): 1221-1229

    Abstract

    BetP is an Na(+)-coupled betaine-specific transporter of the betaine-choline-carnitine (BCC) transporter family involved in the response to hyperosmotic stress. The crystal structure of BetP revealed an overall fold of two inverted structurally related repeats (LeuT-fold) that BetP shares with other sequence-unrelated Na(+)-coupled symporters. Numerous structures of LeuT-fold transporters in distinct conformational states have contributed substantially to our understanding of the alternating access mechanism of transport. Nevertheless, coupling of substrate and co-transported ion fluxes has not been structurally corroborated to the same extent. We converted BetP by a single-point mutation--glycine to aspartate--into an H(+)-coupled choline-specific transporter and solved the crystal structure of this mutant in complex with choline. The structure of BetP-G153D demonstrates a new inward-facing open conformation for BetP. Choline binding to a location close to the second, low-affinity sodium-binding site (Na2) of LeuT-fold transporters is facilitated by the introduced aspartate. Our data confirm the importance of a cation-binding site in BetP, playing a key role in a proposed molecular mechanism of Na(+) and H(+) coupling in BCC transporters.

    View details for DOI 10.1038/emboj.2011.46

    View details for Web of Science ID 000290305200007

    View details for PubMedID 21364531

  • Substrate specificity and ion coupling in the Na+/betaine symporter BetP The EMBO Journal Camilo Perez, Caroline Koshy, Susanne Ressl, Sascha Nicklisch, Reinhard Kr_mer, Christine Ziegler 2011; 30: 1221
  • Molecular basis of transport and regulation in the Na(+)/betaine symporter BetP. Nature Ressl S., Terwisscha van Scheltinga AC, Vonrhein C, Ott V, Ziegler C. 2009; 458: 47

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