2KHT

NMR Structure of human alpha defensin HNP-1

Summary for 2KHT

• Entry DOI: 10.2210/pdb2kht/pdb
• NMR Information: BMRB: 16254
• Descriptor: Neutrophil defensin 1 (1 entity in total)
• Functional Keywords: microcrystalline protein, human alpha defensin, defensin, secreted, antibiotic, antiviral defense, fungicide, phosphoprotein, antimicrobial protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 3452.11

Authors

Zhang, Y.,Li, S.,Doherty, T.F.,Lubkowski, J.,Lu, W.,Li, J.,Barinka, C.,Hong, M. (deposition date: 2009-04-11, release date: 2010-02-09, Last modification date: 2024-05-01)

Primary citation

Zhang, Y.,Doherty, T.,Li, J.,Lu, W.,Barinka, C.,Lubkowski, J.,Hong, M.
Resonance assignment and three-dimensional structure determination of a human alpha-defensin, HNP-1, by solid-state NMR.
J.Mol.Biol., 397:408-422, 2010

PubMed Abstract: 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, (13)C and (15)N 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 HNP interaction with the phospholipid membrane of microbial cells.

PubMed: 20097206
DOI: 10.1016/j.jmb.2010.01.030

Experimental method

SOLID-STATE NMR