Project Details
Projekt
Structural Basis of Z-disc Protein/Protein Networks and Functional Implications
Applicant
Professor Matthias Wilmanns, Ph.D.
Subject Area
Structural Biology
Term
from 2010 to 2017
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 148688621
The giant filament protein titin is central in anchoring, assembling and maintaining the overall architecture of the sarcomeric Z-disc interactome. Here we would like to explore the complete titin Z-disc titin interactome by an integrated approach aiming for structural characterization (our key competence) and functional characterization (with P1, P3, P8). The technologies provided by P7 (electron tomography) will allow us to fit our high-resolution data into integrated images of the complete sarcomeric Z-disc architecture. During the first funding period, we propose to focus on two key Z-disc filament assemblies, titin/α-actinin (with P6) and titin/obscurin. For the first project, our key aim is to unravel the molecular basis and stoichiometry of the α-actinin Z-bridges in relation to the titin Z-disc filament. The second project will allow establishing the molecular basis of an obscurin-mediated connection of the sarcomeric Z-disc interactome to extra-sarcomeric structures and reconstituting important GTPase-mediated signaling pathways that take place in the sarcomeric Z-disc. In parallel (with P4), we will search for novel titin-ligand interactions, using proteomics approaches. We also offer our unique infrastructures for structural biology-oriented collaborations (P2, P10).
DFG Programme
Research Units
