The Neuroendocrine Protein 7B2 Is Intrinsically Disordered

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  • Indrani Dasgupta, Department of Anatomy and Neurobiology, School of Medicine, University of Maryland−Baltimore, USA
  • Laura Sanglas, Department of Anatomy and Neurobiology, School of Medicine, University of Maryland−Baltimore, USA
  • Jan Johannes Enghild
  • Iris Lindberg, Department of Anatomy and Neurobiology, School of Medicine, University of Maryland−Baltimore, USA
The small neuroendocrine protein 7B2 has been shown to be required for the productive maturation of proprotein convertase 2 (proPC2) to an active enzyme form; this action is accomplished via its ability to block aggregation of proPC2 into nonactivatable forms. Recent data show that 7B2 can also act as a postfolding chaperone to block the aggregation of a number of other proteins, for example, α-synuclein. To gain insight into the mechanism of action of 7B2 in blocking protein aggregation, we performed structural studies of this protein using gel filtration chromatography, intrinsic tryptophan fluorescence, 1-anilino-8-naphthalenesulfonate (ANS) binding, circular dichroism (CD), and nuclear magnetic resonance (NMR) spectroscopy. Gel filtration studies indicated that 7B2 exists as an extended monomer, eluting at a molecular mass higher than that expected for a globular protein of similar size. However, chemical cross-linking showed that 7B2 exhibits concentration-dependent oligomerization. CD experiments showed that both full-length 27 kDa 7B2 and the C-terminally truncated 21 kDa form lack appreciable secondary structure, although the longer protein exhibited more structural content than the latter, as demonstrated by intrinsic and ANS fluorescence studies. NMR spectra confirmed the lack of structure in native 7B2, but a disorder-to-order transition was observed upon incubation with one of its client proteins, α-synuclein. We conclude that 7B2 is a natively disordered protein whose function as an antiaggregant chaperone is likely facilitated by its lack of appreciable secondary structure and tendency to form oligomers.
OriginalsprogEngelsk
TidsskriftBiochemistry
Vol/bind51
Nummer38
Sider (fra-til)7456–7464
Antal sider9
ISSN0006-2960
DOI
StatusUdgivet - 4 sep. 2012

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