The N-terminal of NBPF15 causes multiple types of aggregates and mediates phase transition.

In this study, we synthesized and expressed full-length NBPF15, and purified a range of NBPF15 truncations which were analyzed using dynamic light scattering (DLS), superdex200 (S200), small angle X-ray scattering (SAXS), far-UV circular dichroism (CD) spectroscopy, transmission electron microscope (TEM), and crystallography. We found that proteins containing both the N-terminal region and Olduvai domain are heterogeneous with multiple types of aggregates, and some of them underwent a liquid-to-solid phase transition, probably because of the entanglement within the N-terminal coiled-coil. Proteins that contain only the Olduvai domain are homogeneous extended monomers, and those with the conserved clade 1 (CON1) have manifested a tendency to crystallize. We suggest that the entanglements between the mosaic disorder-ordered segments in NBPF15 N terminus have triggered the multiple types of aggregates and phase transition of NBPF15 proteins, which could be associated with Olduvai-related cognitive dysfunction diseases. PMID: 31808794 [PubMed - as supplied by publisher]
Source: The Biochemical Journal - Category: Biochemistry Authors: Tags: Biochem J Source Type: research