Two latent and two hyperstable polymeric forms of human neuroserpin

Matteo Levantino, Maria Grazia Santangelo, Mauro Manno, Martino Bolognesi, Margherita Pezzullo, Alberto Barbiroli, Stefano Ricagno, Francesco Bonomi

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16 Citazioni (Scopus)

Abstract

Human neuroserpin (hNS) is a serine protease inhibitor that belongs to the serpin superfamily and is expressed in nervous tissues. The serpin fold is generally characterized by a long exposed loop, termed the reactive center loop, that acts as bait for the target protease. Intramolecular insertion of the reactive center loop into the main serpin β-sheet leads to the serpin latent form. As with other known serpins, hNS pathological mutants have been shown to accumulate as polymers composed of quasi-native protein molecules. Although hNS polymerization has been intensely studied, a general agreement about serpin polymer organization is still lacking. Here we report a biophysical characterization of native hNS that is shown to undergo two distinct conformational transitions, at 55°C and 85°C, both leading to distinct latent and polymeric species. The latent and polymer hNS forms obtained at 45°C and 85°C differ in their chemical and thermal stabilities; furthermore, the hNS polymers also differ in size and morphology. Finally, the 85°C polymer shows a higher content of intermolecular β-sheet interactions than the 45°C polymer. Together, these results suggest a more complex conformational scenario than was previously envisioned, and, in a general context, may help reconcile the current contrasting views on serpin polymerization.
Lingua originaleEnglish
pagine (da-a)3402-3411
Numero di pagine10
RivistaBiophysical Journal
Volume99
Stato di pubblicazionePublished - 2010

All Science Journal Classification (ASJC) codes

  • Biophysics

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    Levantino, M., Santangelo, M. G., Manno, M., Bolognesi, M., Pezzullo, M., Barbiroli, A., Ricagno, S., & Bonomi, F. (2010). Two latent and two hyperstable polymeric forms of human neuroserpin. Biophysical Journal, 99, 3402-3411.