Dataset Information

The helical structure of surfactant peptide KL4 when bound to POPC: POPG lipid vesicles.

ABSTRACT: KL 4 is a 21-residue peptide employed as a functional mimic of lung surfactant protein B, which successfully lowers surface tension in the alveoli. A mechanistic understanding of how KL 4 affects lipid properties has proven elusive as the secondary structure of KL 4 in lipid preparations has not been determined at high resolution. The sequence of KL 4 is based on the C-terminus of SP-B, a naturally occurring helical protein that binds to lipid interfaces. The spacing of the lysine residues in KL 4 precludes the formation of a canonical amphipathic alpha-helix; qualitative measurements using Raman, CD, and FTIR spectroscopies have given conflicting results as to the secondary structure of the peptide as well as its orientation in the lipid environment. Here, we present a structural model of KL 4 bound to lipid bilayers based on solid state NMR data. Double-quantum correlation experiments employing (13)C-enriched peptides were used to quantitatively determine the backbone torsion angles in KL 4 at several positions. These measurements, coupled with CD experiments, verify the helical nature of KL 4 when bound to lipids, with (phi, psi) angles that differ substantially from common values for alpha-helices of (-60, -45). The average torsion angles found for KL 4 bound to POPC:POPG lipid vesicles are (-105, -30); this deviation from ideal alpha-helical structure allows KL 4 to form an amphipathic helix at the lipid interface.

SUBMITTER: Mills FD

PROVIDER: S-EPMC2629594 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The helical structure of surfactant peptide KL4 when bound to POPC: POPG lipid vesicles.

Mills Frank D FD Antharam Vijay C VC Ganesh Omjoy K OK Elliott Doug W DW McNeill Seth A SA Long Joanna R JR

Biochemistry 20080718 32

KL 4 is a 21-residue peptide employed as a functional mimic of lung surfactant protein B, which successfully lowers surface tension in the alveoli. A mechanistic understanding of how KL 4 affects lipid properties has proven elusive as the secondary structure of KL 4 in lipid preparations has not been determined at high resolution. The sequence of KL 4 is based on the C-terminus of SP-B, a naturally occurring helical protein that binds to lipid interfaces. The spacing of the lysine residues in KL ...[more]

PMID: 18636713

Similar Datasets

Project description:Pulmonary surfactant protein B (SP-B) is an essential protein for lowering surface tension in the alveoli. SP-B(1-25), a peptide comprised of the N-terminal 25 amino-acid residues of SP-B, is known to retain much of the biological activity of SP-B. Circular dichroism has shown that when SP-B(1-25) interacts with negatively charged lipid vesicles, it contains significant helical structure for the lipid compositions and peptide/lipid ratios studied here. The effect of SP-B(1-25) on lipid organization and polymorphisms was investigated via DSC, dynamic light scattering, transmission electron microscopy, and solid-state NMR spectroscopy. At 1-3 mol% peptide and physiologic temperature, SP-B(1-25) partitions at the interface of negatively charged PC/PG lipid bilayers. In lipid mixtures containing 1-5 mol% peptide, the structure of SP-B(1-25) remains constant, but (2)H and (31)P NMR spectra show the presence of an isotropic lipid phase in exchange with the lamellar phase below the T(m) of the lipids. This behavior is observed for both DPPC/POPG and POPC/POPG lipid mixtures as well as for both the PC and PG components of the mixtures. For 1-3 mol% SP-B(1-25), a return to a single lamellar phase above the lipid mixture T(m) is observed, but for 5 mol% SP-B(1-25) a significant isotropic component is observed at physiologic temperatures for DPPC and exchange broadening is observed in (2)H and (31)P NMR spectra of the other lipid components in the two mixtures. DLS and TEM rule out the formation of micellar structures and suggest that SP-B(1-25) promotes the formation of a fluid isotropic phase. The ability of SP-B(1-25) to fuse lipid lamellae via this mechanism, particularly those enriched in DPPC, suggests a specific role for the highly conserved N-terminus of SP-B in the packing of lipid lamellae into surfactant lamellar bodies or in stabilizing multilayer structures at the air-liquid interface. Importantly, this behavior has not been seen for the other SP-B fragments of SP-B(8-25) and SP-B(59-80), indicating a critical role for the proline rich first seven amino acids in this protein.

Dataset Information

The helical structure of surfactant peptide KL4 when bound to POPC: POPG lipid vesicles.

Publications

The helical structure of surfactant peptide KL4 when bound to POPC: POPG lipid vesicles.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets