The helical structure of surfactant peptide KL4 when bound to POPC: POPG lipid vesicles.
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.
Mills
Frank D
FD
Department of Biochemistry and Molecular Biology and McKnight Brain Institute, University of Florida, Box 100245, Gainesville, Florida 32610-0245, USA.
Antharam
Vijay C
VC
Ganesh
Omjoy K
OK
Elliott
Doug W
DW
McNeill
Seth A
SA
Long
Joanna R
JR
D000595:Amino Acid Sequence; D001665:Binding Sites; D036341:Intercellular Signaling Peptides and Proteins; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis* / Q000378:metabolism; D010713:Phosphatidylcholines / Q000737:chemistry* / Q000378:metabolism; D010715:Phosphatidylglycerols / Q000737:chemistry* / Q000378:metabolism; D017433:Protein Structure, Secondary; D011663:Pulmonary Surfactants / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism
D036341:Intercellular Signaling Peptides and Proteins; C097558:KL4 surfactant; D008051:Lipid Bilayers; D010455:Peptides; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D011663:Pulmonary Surfactants; C060037:1-palmitoyl-2-oleoylglycero-3-phosphoglycerol; C028694:1-palmitoyl-2-oleoylphosphatidylcholine