Identification of a segment in the precursor of pulmonary surfactant protein SP-B, potentially involved in pH-dependent membrane assembly of the protein.
In the present work, the hydrophobic properties of proSP-B, the precursor of pulmonary surfactant protein SP-B, have been analyzed under different pH conditions, and the sequence segment at position 111-135 of the N-terminal domain of the precursor has been detected as potentially possessing pH-dependent hydrophobic properties. We have studied the structure and lipid-protein interactions of the synthetic peptides BpH, with sequence corresponding to the segment 111-135 of proSP-B, and BpH-W, bearing the conservative substitution F127W to use the tryptophan as an intrinsic fluorescent probe. Peptide BpH-W interacts with both zwitterionic and anionic phospholipid vesicles at neutral pH, as monitored by the blue-shifted maximum emission of its tryptophan reporter. Insertion of tryptophan into the membranes is further improved at pH 5.0, especially in negatively-charged membranes. Peptides BpH and BpH-W also showed pH-dependent properties to insert into phospholipid monolayers. We have also found that the single sequence variation F120K decreases substantially the interaction of this segment with phospholipid surfaces as well as its pH-dependent insertion into deeper regions of the membranes. We hypothesize that this region could be involved in pH-triggered conformational changes occurring in proSP-B along the exocytic pathway of surfactant in type II cells, leading to the exposure of the appropriate segments for processing and assembly of SP-B within surfactant lipids.
Serrano
Alicia G
AG
Dept. Bioquímica y Biología Molecular I, Facultad de Biología, Universidad Complutense, 28040 Madrid, Spain.
Cabré
Elisa J
EJ
Pérez-Gil
Jesús
J
D000595:Amino Acid Sequence; D002021:Buffers; D002942:Circular Dichroism; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000378:metabolism*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D010743:Phospholipids / Q000494:pharmacology; D011312:Pressure; D011485:Protein Binding / Q000187:drug effects; D011498:Protein Precursors / Q000737:chemistry* / Q000378:metabolism*; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D037701:Pulmonary Surfactant-Associated Protein B / Q000737:chemistry* / Q000378:metabolism*; D012996:Solutions; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship; D017186:Titrimetry; D014867:Water / Q000378:metabolism
D002021:Buffers; D008051:Lipid Bilayers; D010446:Peptide Fragments; D010743:Phospholipids; D011498:Protein Precursors; D037701:Pulmonary Surfactant-Associated Protein B; D012996:Solutions; D014867:Water