Generation of Alzheimer disease-associated amyloid β42/43 peptide by γ-secretase can be inhibited directly by modulation of membrane thickness.

Pathogenic generation of amyloid β-peptide (Aβ) by sequential cleavage of β-amyloid precursor protein (APP) by β- and γ-secretases is widely believed to causally underlie Alzheimer disease (AD). β-Secretase initially cleaves APP thereby generating a membrane-bound APP C-terminal fragment, from which γ-secretase subsequently liberates 37-43-amino acid long Aβ species. Although the latter cleavages are intramembranous and although lipid alterations have been implicated in AD, little is known of how the γ-secretase-mediated release of the various Aβ species, in particular that of the pathogenic longer variants Aβ(42) and Aβ(43), is affected by the lipid environment.

Hsp12 is an intrinsically unstructured stress protein that folds upon membrane association and modulates membrane function.

Hsp12 of S. cerevisiae is upregulated several 100-fold in response to stress. Our phenotypic analysis showed that this protein is important for survival of a variety of stress conditions, including high temperature.

Cloning, purification, crystallization and preliminary crystallographic analysis of SecA from Enterococcus faecalis.

The gene coding for SecA from Enterococcus faecalis was cloned and overexpressed in Escherichia coli. In this protein, the lysine at position 6 was replaced by an asparagine in order to reduce sensitivity towards proteases. The modified protein was purified and crystallized.

The oligomeric distribution of SecYEG is altered by SecA and translocation ligands.

The multimeric membrane protein complex translocase mediates the transport of preproteins across and integration of membrane proteins into the inner membrane of Escherichia coli. The translocase consists of the peripheral membrane-associated ATPase SecA and the heterotrimeric channel-forming complex consisting of SecY, SecE and SecG. We have investigated the quaternary structure of the SecYEG complex in proteoliposomes.

Determination of liposome size: a tool for protein reconstitution.

Reconstitution of proteins into liposomes is a widespread approach to analyzing their biological function. Many protocols exist for this procedure and for the subsequent analysis of proteins. Here, we establish a procedure for preparation and analysis of liposomes with a lipid composition reflecting the outer envelope of chloroplasts.