Journal
JOURNAL OF MOLECULAR BIOLOGY
Volume 397, Issue 2, Pages 408-422Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2010.01.030
Keywords
human alpha-defensin; solid-state NMR; resonance assignment; structure determination; antimicrobial peptides
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Funding
- NIH [GM66976]
- [P41-EB-002026]
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Human alpha-defensins [human neutrophil peptides (HNPs)] are immune defense mini-proteins that act by disrupting microbial cell membranes. Elucidating the three-dimensional (3D) structures of HNPs in lipid membranes is important for understanding their mechanisms of action. Using solid-state NMR (SSNMR), we have determined the 3D structure of HNP-1 in a microcrystalline state outside the lipid membrane, which provides benchmarks for structure determination and comparison with the membrane-bound state. From a suite of two-dimensional and 3D magic-angle spinning experiments, C-13 and N-15 chemical shifts that yielded torsion angle constraints were obtained, while inter-residue distances were obtained to restrain the 3D fold. Together, these constraints led to the first high-resolution SSNMR structure of a human defensin. The SSNMR structure has close similarity to the crystal structures of the HNP family, with the exception of the loop region between the first and second beta-strands. The difference, which is partially validated by direct torsion angle measurements of selected loop residues, suggests possible conformational variation and flexibility of this segment of the protein, which may regulate HNF interaction with the phospholipid membrane of microbial cells. (C) 2010 Elsevier Ltd. All rights reserved.
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