Modifications to Surfactant Protein B Structure and Lipid Interactions Under Ards Conditions: Consequences of Tryptophan Oxidation

Abstract

Oxidation of Surfactant Protein B (SP-B) is one of several mechanisms proposed to lead to inactivation of lung surfactant in patients with Acute Respiratory Distress Syndrome (ARDS). We have used solution NMR, circular dichroism and molecular dynamics simulation to explore the consequences of oxidation of the tryptophan residue in fragments of SP-B. These fragments include the N-terminal helix of SP-B, as well as Mini-B, a fragment that includes both the N-and C-terminal helices. The fragments were studied in a number of conditions including aqueous solution, organic solvent, zwitterionic and anionic micelles, as well as monolayers. Tryptophan oxidation was found to result in both the partial loss of α-helical structure, as well as differences in peptide positioning with respect to the lipids.