Integrated solid-state NMR and molecular dynamics modeling determines membrane insertion of human β-defensin analog.

ABSTRACT: Human β-defensins (hBD) play central roles in antimicrobial activities against various microorganisms and in immune-regulation. These peptides perturb phospholipid membranes for function, but it is not well understood how defensins approach, insert and finally disrupt membranes on the molecular level. Here we show that hBD-3 analogs interact with lipid bilayers through a conserved surface that is formed by two adjacent loops in the solution structure. By integrating a collection of ¹³C, ¹H and ³¹P solid-state NMR methods with long-term molecular dynamic simulations, we reveal that membrane-binding rigidifies the peptide, enhances structural polymorphism, and promotes β-strand conformation. The peptide colocalizes with negatively charged lipids, confines the

SUBMITTER: Kang X 

PROVIDER: S-EPMC6825183 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature