Alzheimer's Disease - structure of gamma-secretase complex
Presenilin-1 (PS-1) is a catalytic component of the membranous complex of γ-secretase which plays an important role in onset and development of Alzheimer’s Disease. It cuts the APP (Amyloid Precursor Protein) to β-amyloid which can aggregate in neurons. The γ-secretase complex consists of four proteins: PS1, APH-1, PEN-2 and nicastrin (Nct). Structures of all of these proteins are unknown. In the maturation process the structure of PS-1 is cleaved on N- and C-terminal fragments (NTF and CTF). Structure of CTF was determined using NMR methods in detergent micelles (Sobhanifar et al., PNAS 2010). Our group revealed how this structure is changing in a micelle of detergent molecules as well as in lipid bilayers (DLPC, DPPC and implicit) using different types of molecular dynamics simulations. This research is continued toward determination of interactions with the substrate APP and drug design.
(Cooperation with BioNMR Centre at Goethe University, Frankfurt/Main, Germany)
The latest news
The ERNEST project (COST CA18133) has started.
ERNEST = European Research Network on Signal Transduction
The main scientific objective of the Action is to develop a common, comprehensive and holistic map of signal transduction that will advance development of pathway-specific chemical modulators. This unique and innovative goal will be realised by linking of a diverse group of researchers in the field through the networking activities funded by COST.
Our service GPCRM is completely reshaped, much faster, and user friendly. Now, it contains 3 main routes: Quick path (default), Long path, and High similarity (the fastest) for homology modeling of GPCRs. Currently, the service contains over 90 template structures. The updated version was recently published in NAR 2018, W1.