More than a third of the proteins of any cell are exported from the cytoplasm to cellular membranes or across them. This is an essential cellular process and over two thirds of drugs in use target plasma membrane proteins. To reach the membrane, secretory proteins make use of aminoterminal signal peptides and novel signals that we recently identified in their mature domains. These uncharacterized signals are exposed only in natively unfolded states. Cellular machineries would have to decipher this “non-native code”. Nonaco aims to identify the molecular nature of these signals and their interplay with signal peptides. Also, it will identify the global network of cellular factors that usher preproteins from the ribosome to the membrane. To this end a team of international experts will employ protein to proteome-level dissection. This involves a multi-disciplinary battery of tools that combine bioinformatics, biophysics, structural biology, mass spectrometry, molecular biology and enzymology. Nonaco aims to elucidate a fundamental biological process by analyzing fascinating new features of the process and contribute towards our understanding of trafficking and misfolding disease.

Computer Model of a Natively Unfolded Protein (credit)