1rg4

From Proteopedia

Revision as of 11:51, 20 March 2008

SP-B C-terminal peptide in organic solvent (HFIP)

Overview

Although the membrane-associated surfactant protein B (SP-B) is an essential component of lung surfactant, which is itself essential for life, the molecular basis for its activity is not understood. SP-B's biophysical functions can be partially mimicked by subfragments of the protein, including the C-terminus. We have used NMR to determine the structure of a C-terminal fragment of human SP-B that includes residues 63-78. Structure determination was performed both in the fluorinated alcohol hexafluoro-2-propanol (HFIP) and in sodium dodecyl sulfate (SDS) micelles. In both solvents, residues 68-78 take on an amphipathic helical structure, in agreement with predictions made by comparison to homologous saposin family proteins. In HFIP, the five N-terminal residues of the peptide are largely unstructured, while in SDS micelles, these residues take on a well-defined compact conformation. Differences in helical residue side chain positioning between the two solvents were also found, with better agreement between the structures for the hydrophobic face than the hydrophilic face. A paramagnetic probe was used to investigate the position of the peptide within the SDS micelles and indicated that the peptide is located at the water interface with the hydrophobic face of the helix oriented inward, the hydrophilic face of the helix oriented outward, and the N-terminal residues even farther from the micelle center than those on the hydrophilic face of the alpha-helix. Interactions of basic residues of SP-B with anionic lipid headgroups are known to have an impact on function, and these studies demonstrate structural ramifications of such interactions via the differences observed between the peptide structures determined in HFIP and SDS.

Disease

Known disease associated with this structure: Surfactant metabolism dysfunction, pulmonary, 1 OMIM:[178640]

About this Structure

1RG4 is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.

Reference

NMR structures of the C-terminal segment of surfactant protein B in detergent micelles and hexafluoro-2-propanol., Booth V, Waring AJ, Walther FJ, Keough KM, Biochemistry. 2004 Dec 7;43(48):15187-94. PMID:15568810

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