Department of Cell Biology
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Imagine a big city without a car driving and no mail being delivered. The resulting chaos is similar to what happens to a cell when its molecular transport systems are impaired. Our goal is to understand the molecular principles underlying cargo recognition by transport complexes, complex assembly and activation, and eventually complex disassembly after the transport. Our research tools are X-ray crystallography, quantitative biophysical approaches, biochemistry, and in vivo studies.

As our main model system, we analyze the directional transport of ASH1 mRNA in S. cerevisiae. Besides mRNA, this cargo-transport complex consists of the myosin motor Myo4p, its bound adapter She3p, and the RNA-cargo binding protein She2p. We determined crystal structures of She2p and Myo4p, and performed functional analysis on the assembly of this complex. Recently, we succeeded in reconstituting functional subcomplexes that allowed us to understand how specific recognition of cargo RNA is achieved.

 

 

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FIG. 1: ASH1 mRNA transport complex. Taken from Heym & Niessing, Cell Mol Life Sci (2012).

We also study transport factors from neurons. For instance, we determined the crystal structure of the neuronal RNA-binding protein Pur-alpha and showed by SAXS that it adopts an unusual topology in solution. At the department of Cell Biology, we continue our work on neuronal mRNA transport in collaboration with the Kiebler lab.

Our long-term goal is to understand how core factors of large multiprotein complexes interact to (i) detect their cargo, (ii) assemble into functional complexes in response to cargo recognition and (iii) translocate their cargo through the cytoplasm.

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A second research focus is to understand posttranscriptional gene regulation at the level of mRNA stability. Here we collaborate with the groups of Vigo Heissmeyer (LMU & HMGU) and Michael Sattler (TU München & HMGU) on the structure-to-functional analysis of the T-cell specific factor Roquin and its RNA targets (Schlundt et al, NSMB 2014).

 

 

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FIG. 2: Co-structure of ROQ domain of Roquin in complex with its RNA target, the canonical decay element (CDE) in the Tnf mRNA (resolution 3.0 Å, Rfree = 24.7%). Taken from Schlundt et al. NSMB (2014).
In another project, we studied the interaction of Ago2 with its adapter protein TNRC6C and clarified their mode of interaction (collaboration with Gunter Meister, Regensburg; Pfaff et al, PNAS 2013).