On the molecular structure of human neuroserpin polymers
Article first published online: 9 NOV 2011
Copyright © 2011 Wiley Periodicals, Inc.
Proteins: Structure, Function, and Bioinformatics
Volume 80, Issue 1, pages 8–13, January 2012
How to Cite
Santangelo, M. G., Noto, R., Levantino, M., Cupane, A., Ricagno, S., Pezzullo, M., Bolognesi, M., Mangione, M. R., Martorana, V. and Manno, M. (2012), On the molecular structure of human neuroserpin polymers. Proteins, 80: 8–13. doi: 10.1002/prot.23197
- Issue published online: 13 DEC 2011
- Article first published online: 9 NOV 2011
- Accepted manuscript online: 19 SEP 2011 04:59AM EST
- Manuscript Accepted: 14 SEP 2011
- Manuscript Revised: 4 SEP 2011
- Manuscript Received: 22 JUL 2011
- protein aggregation;
- serpin polymerization;
The polymerization of serpins is at the root of a large class of diseases; the molecular structure of serpin polymers has been recently debated. In this work, we study the polymerization kinetics of human neuroserpin by Fourier Transform Infra Red spectroscopy and by time-lapse Size Exclusion Chromatography. First, we show that two distinct neuroserpin polymers, formed at 45 and 85°C, display the same isosbestic points in the Amide I′ band, and therefore share common secondary structure features. We also find a concentration independent polymerization rate at 45°C suggesting that the polymerization rate-limiting step is the formation of an activated monomeric species. The polymer structures are consistent with a model that predicts the bare insertion of portions of the reactive center loop into the A β-sheet of neighboring serpin molecule, although with different extents at 45 and 85°C. Proteins 2012; © 2011 Wiley Periodicals, Inc.