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The N-terminal of NBPF15 causes multiple types of aggregates and mediates phase transition.
Biochem J, 477(2):445-458.
The neuroblastoma breakpoint family (NBPF) consists of 24 members that play animportant role in neuroblastoma and other cancers. NBPF is an evolutionarilyrecent gene family that encodes several repeats of Olduvai domain and an abundantN-terminal region. The function and biochemical properties of both Olduvai domainand the N-terminal region remain enigmatic. Human NBPF15 encodes a 670 AA proteinconsisting of six clades of Olduvai domains. In this study, we synthesized andexpressed full-length NBPF15, and purified a range of NBPF15 truncations whichwere 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 thatproteins containing both the N-terminal region and Olduvai domain areheterogeneous with multiple types of aggregates, and some of them underwent aliquid-to-solid phase transition, probably because of the entanglement within theN-terminal coiled-coil. Proteins that contain only the Olduvai domain arehomogeneous extended monomers, and those with the conserved clade 1 (CON1) havemanifested a tendency to crystallize. We suggest that the entanglements betweenthe mosaic disorder-ordered segments in NBPF15 N terminus have triggered themultiple types of aggregates and phase transition of NBPF15 proteins, which couldbe associated with Olduvai-related cognitive dysfunction diseases.
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