The pulmonary surfactant protein C (SP-C) precursor is a type II transmembrane protein (original) (raw)
Related papers
Biochemical Journal, 2011
Proteins SP-B and SP-C are essential to promote formation of surface-active films at the respiratory interface, but their mechanism of action is still under investigation. In the present study we have analysed the effect of the proteins on the accessibility of native, quasi-native and model surfactant membranes to incorporation of the fluorescent probes Nile Red (permeable) and FM 1-43 (impermeable) into membranes. We have also analysed the effect of single or combined proteins on membrane permeation using the soluble fluorescent dye calcein. The fluorescence of FM 1-43 was always higher in membranes containing SP-B and/or SP-C than in protein-depleted membranes, in contrast with Nile Red which was very similar in all of the materials tested. SP-B and SP-C promoted probe partition with markedly different kinetics. On the other hand, physiological proportions of SP-B and SP-C caused giant oligolamellar vesicles to incorporate FM 1-43 from the external medium into apparently most of t...
Secretion of Surfactant Protein C, an Integral Membrane Protein, Requires the N-terminal Propeptide
Journal of Biological Chemistry, 2001
Proteolytic processing of surfactant protein C (SP-C) proprotein in multivesicular bodies of alveolar type II cells results in a 35-residue mature peptide, consisting of a transmembrane domain and a 10-residue extramembrane domain. SP-C mature peptide is stored in lamellar bodies (a lysosomal-like organelle) and secreted with surfactant phopholipids into the alveolar space. This study was designed to identify the peptide domain of SP-C required for sorting and secretion of this integral membrane peptide. Deletion analyses in transiently transfected PC12 cells and isolated mouse type II cells suggested the extramembrane domain of mature SP-C was cytosolic and sufficient for sorting to the regulated secretory pathway. Intratracheal injection of adenovirus encoding SP-C mature peptide resulted in secretion into the alveolar space of wild type mice but not SP-C (؊/؊) mice. SP-C secretion in null mice was restored by the addition of the N-terminal propeptide. The cytosolic domain, consisting of the Nterminal propeptide and extramembrane domain of mature SP-C peptide, supported secretion of the transmembrane domain of platelet-derived growth factor receptor. Collectively, these studies indicate that the N-terminal propeptide of SP-C is required for intracellular sorting and secretion of SP-C.
The role of pulmonary surfactant protein C during the breathing cycle
Thin Solid Films, 1998
A model pulmonary surfactant consisting of dipalmitoylphosphatidylcholine, dipalmitoylphosphatidylglycerol, and the surfactant associated protein C (SP-C) was investigated by film balance measurements. The surface of the film balance should mimic the air-liquid interface of the lung. In order to visualize their chemical and topographical structure surface films formed from the model surfactant were investigated by fluorescence light microscopy (FLM) and, after transfer to a solid substrate, by time-of-flight secondary ion mass spectrometry (TOF-SIMS) and scanning force microscopy (SFM). The FLM images of the system revealed that in an early stage of compression phase separation into a protein-rich phase and a pure lipid phase occurred. In the region of physiological surface tensions the course of the isotherm showed a plateau with extremely high compressibility. By SFM the formation of stacks of lipid bilayers which was reversible on expansion was detected in the plateau region. From FLM and TOF-SIMS we revealed that these structures are enriched in SP-C. We developed a molecular model of the multilayer structure. According to that, SP-C spans a single bilayer with its long axes in parallel to the membrane normal. It stabilizes, or destabilizes, respectively, the bilayer stacks according to the phase of the breathing cycle.
Biochimica et Biophysica Acta (BBA) - Biomembranes, 2005
Pulmonary surfactant protein SP-C is a 35-residue polypeptide composed of a hydrophobic transmembrane alpha-helix and a polycationic, palmitoylated-cysteine containing N-terminal segment. This segment is likely the only structural motif the protein projects out of the bilayer in which SP-C is inserted and is therefore a candidate motif to participate in interactions with other bilayers or monolayers. In the present work, we have detected intrinsic ability of a peptide based on the sequence of the N-terminal segment of SP-C to interact and insert spontaneously into preformed zwitterionic or anionic phospholipid monolayers. The peptide expands the k-A compression isotherms of interfacial phospholipid/peptide films, and perturbs the lipid packing of phospholipid films during compression-driven liquid-expanded to liquid-condensed lateral transitions, as observed by epifluorescence microscopy. These results demonstrate that the sequence of the SP-C Nterminal region has intrinsic ability to interact with, insert into, and perturb the structure of zwitterionic and anionic phospholipid films, even in the absence of the palmitic chains attached to this segment in the native protein. This effect has been related with the ability of SP-C to facilitate reinsertion of surface active lipid molecules into the lung interface during respiratory compression-expansion cycling.
Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, 2001
Predictive studies suggest that the known sequences of the N-terminal segment of surfactant protein SP-C from animal species have an intrinsic tendency to form -turns, but there are important differences on the probable location of these motifs in different SP-C species. Our hypothesis is that intrinsic structural determinants of the sequence of the N-terminal region of SP-C could define conformation, acylation and perhaps surface properties of the mature protein.
Biochemical Journal, 2004
In the present study, 13-residue peptides with sequences corresponding to the native N-terminal segment of pulmonary SP-C (surfactant protein C) have been synthesized and their interaction with phospholipid bilayers characterized. The peptides are soluble in aqueous media but associate spontaneously with bilayers composed of either zwitterionic (phosphatidylcholine) or anionic (phosphatidylglycerol) phospholipids. The peptides show higher affinity for anionic than for zwitterionic membranes. Interaction of the peptides with both zwitterionic and anionic membranes promotes phospholipid vesicle aggregation, and leakage of the aqueous content of the vesicles. The lipid–peptide interaction includes a significant hydrophobic component for both zwitterionic and anionic membranes, although the interaction with phosphatidylglycerol bilayers is also electrostatic in nature. The effects of the SP-C N-terminal peptides on the membrane structure are mediated by significant perturbations of the ...