Startseite Lebenswissenschaften Membrane Activity of (Cys48Ser) Lung Surfactant Protein B Increases with Dimerisation
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Membrane Activity of (Cys48Ser) Lung Surfactant Protein B Increases with Dimerisation

  • Shahparak Zaltash , William J. Griffiths , David Beck , Chen-Xia Duan , Timothy E. Weaver und Jan Johansson
Veröffentlicht/Copyright: 1. Juni 2005
Biological Chemistry
Aus der Zeitschrift Band 382 Heft 6

Abstract

One of the possible functions of lung surfactant protein B (SPB), an hydrophobic membraneassociated saposinlike protein, is to reduce the alveolar surface tension by promoting insertion of phospholipids into the air/liquid interface of the lung. SPB is a covalent homodimer; Cys48 of two polypeptides form an intermolecular disulphide bond. In order to test whether dimerisation of SPB is important for surfactant function, transgenic mice which express (Cys48Ser) human SPB in a mouse SPB null background were generated. In previous studies (Cys48Ser)SPB showed a concentrationdependent in vitro activity, suggesting that it may form noncovalent dimers. Here (Cys48Ser)SPB isolated from bronchoalveolar lavage of transgenic mice was studied at different concentrations by circular dichroism (CD) spectroscopy, pulsating bubble surfactometry, mass spectrometry and reversedphase HPLC. The results indicate that (Cys48Ser)SPB, both in a phospholipid environment and in organic solvents, is largely monomeric and exhibits low activity at concentrations lower than 1 2 M, while at higher concentrations it forms noncovalent dimers, which are nearly functionally equivalent to native SPB in vitro. Furthermore, electrospray mass spectrometry showed that more dimers were found relative to the monomer when the polarity of the solvent was decreased, and when the concentration of SPB increased. (Cys48Ser)SPB also eluted earlier than native SPB in reversedphase HPLC. Taken together, these results indicate that a polar surface is buried upon dimerisation, thereby promoting formation of interchain ion pairs between Glu51 Arg52 and Glu51Arg52.

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Published Online: 2005-06-01
Published in Print: 2001-06-27

Copyright © 2001 by Walter de Gruyter GmbH & Co. KG

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