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J Am Chem Soc. 2013 Apr 24;135(16):6014-7. doi: 10.1021/ja402187t. Epub 2013 Apr 15.

Hydroxyproline-free single composition ABC collagen heterotrimer.

Author information

1
Department of Chemistry, Rice University, 6100 Main Street, Houston, Texas 77005, USA.

Abstract

Hydroxyproline plays a major role in stabilizing collagenous domains in eukaryotic organisms. Lack of this modification is associated with significant lowering in the thermal stability of the collagen triple helix and may also affect fibrillogenesis and folding of the peptide chains. In contrast, even though bacterial collagens lack hydroxyproline, their thermal stability is comparable to that of fibrillar collagen. This has been attributed to the high frequency of charged amino acids found in bacterial collagen. Here we report a thermally stable hydroxyproline-free ABC heterotrimeric collagen mimetic system composed of decapositive and decanegative peptides and a zwitterionic peptide. None of the peptides contain hydroxyproline, and furthermore the zwitterionic peptide does not even contain proline. The heterotrimer is electrostatically stabilized via multiple interpeptide lysine-aspartate and lysine-glutamate salt bridges and maintains good thermal stability with a melting temperature of 37 °C. The ternary peptide mixture also populates a single composition ABC heterotrimer as confirmed by circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy. This system illustrates the power of axial salt bridges to direct and stabilize the self-assembly of a triple helix and may be useful in analogous designs in expression systems where the incorporation of hydroxyproline is challenging.

PMID:
23574286
PMCID:
PMC3663077
DOI:
10.1021/ja402187t
[Indexed for MEDLINE]
Free PMC Article

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