Abstract
Human small EDRK-rich factor protein SERF2 is a cellular driver of protein amyloid formation, a process that has been linked to neurodegenerative diseases including Alzheimer’s and Parkinson’s disease. SERF2 is a 59 amino acid protein, highly charged, and well conserved whose structure and physiological function is unclear. SERF family proteins including human SERF2 have 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. TALOS-N predicted secondary structure of SERF2 showed three very short helices (3–4 residues long) in the N-terminal region of the protein and a long helix in the C-terminal region spanning residues 37–46 which is consistent with the helical content indicated by circular dichroism spectroscopy. Paramagnetic relaxation enhancement NMR analysis revealed that a short C-terminal region E53-K55 is in the proximity of the N-terminus. Having the backbone assignment of SERF2 allowed us to probe its interaction with α-Synuclein and to identify the residues in SERF2 binding interfaces that likely promote α-Synuclein aggregation.
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Data availability
The 1H, 13C, and 15N chemical shifts of human SERF2 has been deposited to the BioMagResBank (www.bmrb.wisc.edu) under the accession number BMRB-52141.
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Acknowledgements
J.C.A.B. is a Howard Hughes Medical Institute (HHMI) Investigator and this study was supported by funds from HHMI.
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This study was supported by funds from Howard Hughes Medical Institute to J.C.A.B.
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B.S. and J.C.A.B. planned the study and designed experiments. B.S. performed experiments. B.S. and V.S. interpreted the results. B.S. and J.C.A.B. wrote the manuscript.
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Sahoo, B.R., Subramanian, V. & Bardwell, J.C. Backbone 1H, 13C, and 15N chemical shift assignments for human SERF2. Biomol NMR Assign (2024). https://doi.org/10.1007/s12104-024-10167-5
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DOI: https://doi.org/10.1007/s12104-024-10167-5