Biology subjects

Hansmann, U.

Publications and source records attributed to Hansmann, U..

4 recordsLinked to original sources

bioRxiv2017

Mutations alter RNA-mediated conversion of human prions

Prion diseases are connected with self-replication and self-propagation of mis-folded proteins. The rate-limiting factor is the formation of the initial seed. We have recently studied early stages in the conversion between functional PrPC and the infectious scrapie PrPSC form, triggered by the binding of RNA. Here, we study how this process is modulated by the prion sequence. We focus on residues 129 and 178, which are connected to the hereditary neurodegenerative disease Fatal Familial Insomnia.

biochemistry↗

bioRxiv2017

Multi-Funnel Landscape of the Fold-Switching Protein RfaH-CTD

Proteins such as the transcription factor RfaH can change biological function by switching between distinct three-dimensional folds. RfaH regulates transcription if the C-terminal domain folds into a double helix bundle, and promotes translation when this domain assumes a {beta}-barrel form. This fold-switch has been also observed for the isolated domain, dubbed by us RfaH-CTD, and is studied here with a variant of the RET approach recently introduced by us. We use the enhanced sampling properties of this technique to map the free energy landscape of RfaH-CTD and to propose a mechanism for the conversion process.\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=109 SRC=\"FIGDIR/small/221143_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (23K):\norg.highwire.dtl.DTLVardef@17ce490org.highwire.dtl.DTLVardef@81ce9aorg.highwire.dtl.DTLVardef@230ddborg.highwire.dtl.DTLVardef@162be94_HPS_FORMAT_FIGEXP M_FIG TOC Image\n\nC_FIG

biochemistry↗

bioRxiv2017

Conversion between parallel and antiparallel β-sheets in wild-type and Iowa mutant fibrils

Using a variant of Hamilton-Replica-Exchange we study for wild type and Iowa mutant A{beta}40 the conversion between fibrils with antiparallel {beta}-sheets, and such with parallel {beta}-sheets. We show that wild type and mutant form distinct salt bridges that in turn stabilize different fibril organizations. The conversion between the two fibril forms leads to the release of small aggregates that in the Iowa mutant may shift the equilibrium from fibrils to more toxic oligomers.

biophysics↗

bioRxiv2017

Out-of-Register Aβ42 Assemblies as Models for Neurotoxic Oligomers and Fibrils

We propose a variant of the recently found S-shaped A{beta}1-42-motif that is characterized by out-of-register C-terminal {beta}-strands. We show that chains with this structure can not only form fibrils that are compatible with the NMR signals, but also barrel-shaped oligomers that resemble the ones formed by the much smaller cylindrin peptides. Running at physiological temperatures long all-atom molecular dynamics simulations with an explicit solvent, we study the stability of these constructs and show that they are plausible models for neurotoxic oligomers. Analyzing the transitions between different assemblies we suggest a mechanism for amyloid formation in Alzheimers disease.

biochemistry↗