Interactions of the C-terminus of lung surfactant protein B with lipid bilayers are modulated by acyl chain saturation.
Lung surfactant protein B (SP-B) is critical to minimizing surface tension in the alveoli. The C-terminus of SP-B, residues 59-80, has much of the surface activity of the full protein and serves as a template for the development of synthetic surfactant replacements. The molecular mechanisms responsible for its ability to restore lung compliance were investigated with circular dichroism, differential scanning calorimetry, and (31)P and (2)H solid-state NMR spectroscopy. SP-B(59-80) forms an amphipathic helix which alters lipid organization and acyl chain dynamics in fluid lamellar phase 4:1 DPPC:POPG and 3:1 POPC:POPG MLVs. At higher levels of SP-B(59-80) in the POPC:POPG lipid system a transition to a nonlamellar phase is observed while DPPC:POPG mixtures remain in a lamellar phase. Deuterium NMR shows an increase in acyl chain order in DPPC:POPG MLVs on addition of SP-B(59-80); in POPC:POPG MLVs, acyl chain order parameters decrease. Our results indicate SP-B(59-80) penetrates deeply into DPPC:POPG bilayers and binds more peripherally to POPC:POPG bilayers. Similar behavior has been observed for KL(4), a peptide mimetic of SP-B which was originally designed using SP-B(59-80) as a template and has been clinically demonstrated to be successful in treating respiratory distress syndrome. The ability of these helical peptides to differentially partition into lipid lamellae based on their degree of monounsaturation and subsequent changes in lipid dynamics suggest a mechanism for lipid organization and trafficking within the dynamic lung environment.
Antharam
Vijay C
VC
Department of Biochemistry and Molecular Biology and McKnight Brain Institute, Box 100245, Gainesville, FL 32610-0245, USA.
Farver
R Suzanne
RS
Kuznetsova
Anna
A
Sippel
Katherine H
KH
Mills
Frank D
FD
Elliott
Douglas W
DW
Sternin
Edward
E
Long
Joanna R
JR
D002152:Calorimetry, Differential Scanning; D002942:Circular Dichroism; D005227:Fatty Acids / Q000737:chemistry*; D008051:Lipid Bilayers / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010715:Phosphatidylglycerols / Q000737:chemistry; D017433:Protein Structure, Secondary; D037701:Pulmonary Surfactant-Associated Protein B / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013696:Temperature; D053835:Unilamellar Liposomes / Q000378:metabolism
D005227:Fatty Acids; D008051:Lipid Bilayers; D010715:Phosphatidylglycerols; D037701:Pulmonary Surfactant-Associated Protein B; D053835:Unilamellar Liposomes; C060037:1-palmitoyl-2-oleoylglycero-3-phosphoglycerol