title: The surfactant peptide KL4 sequence is inserted with a transmembrane orientation into the endoplasmic reticulum membrane.
abstract: Surfactant protein B (SP-B) is an essential component of pulmonary surfactant. Synthetic surfactant peptide KL(4), a peptide based on a C-terminal amphipathic helical region of human SP-B, efficiently mimics some functional properties of SP-B and is included in therapeutic surfactant preparations used in trials to treat respiratory distress syndrome. The membrane orientation of this peptide is controversial. We used an in vitro transcription-translation system to study the insertion of hydrophobic sequences into microsomal membranes, and showed that the KL(4) sequence integrates efficiently with a transmembrane orientation despite the presence of intermittent lysines throughout the sequence. In contrast, the precise sequence of the C-terminal SP-B amphipathic region failed to integrate, indicating a nontransmembrane orientation. Differences in the membrane insertion between KL(4) and the SP-B-inspiring sequence match predictions from calculated free energies of insertion of the two sequences into membranes.
authors.forename: Luis
authors.initials: L
authors.lastname: Martínez-Gil
authors.forename: Jesús
authors.initials: J
authors.lastname: Pérez-Gil
authors.forename: Ismael
authors.initials: I
authors.lastname: Mingarro
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007231:Infant, Newborn; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D037701:Pulmonary Surfactant-Associated Protein B / Q000737:chemistry*
chemical_list: D010455:Peptides; D037701:Pulmonary Surfactant-Associated Protein B