Backbone 1H, 13C, and 15N chemical shift assignments for human SERF2

Abstract

Abstract Human small EDRK-rich factor protein SERF2 is a cellular driver of protein amyloid formation which has been linked to many different neurodegenerative diseases including Alzheimer’s and Parkinson’s disease. SERF2 though tiny (59 residues) and highly charged, its structure and physiological function remains unexplored. SERF family proteins including human SERF2 is shown a tendency to form fuzzy complexes with misfolded proteins such as α-Synuclein which has been linked to Parkinson’s disease. SERF family proteins have been recently identified to bind nucleic acids, but the binding mechanism(s) remain enigmatic. Here, using multidimensional solution NMR, we report the 1H, 15N, and 13C chemical shift assignments (~86 % of backbone resonance assignments) for human SERF2. TALSO-N predicted secondary structure of SERF2 showed three short-helix (3-4 residues long) at N-terminus and a long (region 37-46) which correlates to SERF2’s helical structure observed by circular dichroism spectroscopy. Paramagnetic relaxation enhancement NMR analysis revealed a short C-terminal region E53-K55 is spatially oriented in the proximity of the N-terminus. The backbone assignment of SERF2 led us to probe its interaction with α-Synuclein and identifying key binding interfaces in SERF2 that promote α-Synuclein aggregation.