Trp-26 imparts functional versatility to human α-defensin HNP

Gang Wei, Marzena Pazgier, Erik De Leeuw, Mohsen Rajabi, Jing Li, Guozhang Zou, Grace Jung, Weirong Yuan, Wei Yue Lu, Robert I. Lehrer, Wuyuan Lu

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


We performed a comprehensive alanine scan of human α-defensin HNP1 and tested the ability of the resulting analogs to kill Staphylococcus aureus, inhibit anthrax lethal factor, and bind human immunodeficiency virus-1 gp120. By far, the most deleterious mutation for all of these functions was W26A. The activities lost by W26A-HNP1 were restored progressively by replacing W26 with non-coded, straight-chain aliphatic amino acids of increasing chain length. The hydrophobicity of residue 26 also correlated with the ability of the analogs to bind immobilized wild type HNP1 and to undergo further self-association. Thus, the hydrophobicity of residue 26 is not only a key determinant of the direct interactions ofHNP1with target molecules, but it also governs the ability of this peptide to form dimers and more complex quaternary structures at micromolar concentrations. Although all defensin peptides are cationic, their amphipathicity is at least as important as their positive charge in enabling them to participate in innate host defense.

Original languageEnglish
Pages (from-to)16275-16285
Number of pages11
JournalJournal of Biological Chemistry
Issue number21
StatePublished - 21 May 2010
Externally publishedYes


Dive into the research topics of 'Trp-26 imparts functional versatility to human α-defensin HNP'. Together they form a unique fingerprint.

Cite this