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Solution structure and backbone dynamics of an omega-conotoxin precursor.
D P Goldenberg1, R E Koehn, D E Gilbert
1Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA. goldenberg@biology.utah.edu
Summary
The precursor form of omega-conotoxin MVIIA (omega-MVIIA-Gly) exhibits enhanced folding efficiency due to its terminal glycine residue. This glycine participates in hydrogen bonding, contributing to the peptide
Area of Science:
- Biochemistry
- Structural Biology
- Neuroscience
Background:
- Omega-conotoxin MVIIA is a peptide antagonist of voltage-gated Ca(2+) channels.
- The mature peptide from Conus magus venom has an amidated carboxyl terminus.
- A precursor form, omega-MVIIA-Gly, includes an unmodified terminal glycine.
Purpose of the Study:
- To characterize the solution structure and backbone dynamics of omega-MVIIA-Gly.
- To understand the role of the terminal glycine in folding and stability.
- To investigate the dynamics of a segment implicated in target binding.
Main Methods:
- Nuclear magnetic resonance (NMR) spectroscopy.
- NMR structure determination.
- (15)N relaxation experiments.
Main Results:
- The NMR structure of omega-MVIIA-Gly is similar to the mature form.
- The terminal glycine participates in hydrogen bonding, enhancing stability and folding.
- Residues 9-15 undergo conformational exchange (approx. 35 microseconds), potentially aiding target binding.
Conclusions:
- The terminal glycine in omega-MVIIA-Gly significantly enhances folding efficiency and stability.
- Observed backbone dynamics in residues 9-15 may be crucial for peptide-target interaction.