2esy
From Proteopedia
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Structure and influence on stability and activity of the N-terminal propetide part of lung surfactant protein C
Overview
Mature lung surfactant protein C (SP-C) corresponds to residues 24-58 of, the 21 kDa proSP-C. A late processing intermediate, SP-Ci, corresponding, to residues 12-58 of proSP-C, lacks the surface activity of SP-C, and the, SP-Ci alpha-helical structure does not unfold in contrast to the, metastable nature of the SP-C helix. The NMR structure of an analogue of, SP-Ci, SP-Ci(1-31), with two palmitoylCys replaced by Phe and four Val, replaced by Leu, in dodecylphosphocholine micelles and in ethanol shows, that its alpha-helix vs. that of SP-C is extended N-terminally. The, Arg-Phe part in SP-Ci that is cleaved to generate SP-C is localized in a, turn structure, which is followed by a short segment in extended, conformation. Circular dichroism spectroscopy of SP-Ci(1-31) in microsomal, or surfactant lipids shows a mixture of helical and extended conformation, at pH 6, and a shift to more unordered structure at pH 5. Replacement of, the N-terminal hexapeptide segment SPPDYS (known to constitute a signal in, intracellular targeting) of SP-Ci with AAAAAA results in a peptide that is, mainly unstructured, independent of pH, in microsomal and surfactant, lipids. Addition of a synthetic dodecapeptide, corresponding to the, propeptide part of SP-Ci, to mature SP-C results in slower aggregation, kinetics and altered amyloid fibril formation, and reduces the surface, activity of phospholipid-bound SP-C. These data suggest that the, propeptide part of SP-Ci prevents unfolding by locking the N-terminal part, of the helix, and that acidic pH results in structural disordering of the, region that is proteolytically cleaved to generate SP-C.
About this Structure
2ESY is a Protein complex structure of sequences from [1] with as ligand. Full crystallographic information is available from OCA.
Reference
Structure and influence on stability and activity of the N-terminal propeptide part of lung surfactant protein C., Li J, Liepinsh E, Almlen A, Thyberg J, Curstedt T, Jornvall H, Johansson J, FEBS J. 2006 Mar;273(5):926-35. PMID:16478467
Page seeded by OCA on Tue Jan 29 19:20:24 2008
