The pulmonary surfactant protein C (SP-C) precursor is a type II transmembrane protein.
Human pulmonary-surfactant-associated protein C (SP-C) is an extremely hydrophobic peptide comprising 34-35 amino acids. It is involved in the reduction of surface tension at the air/liquid in the lung. In order to understand the mechanism by which this molecule is generated from its 197-amino-acid-residues-long precursor and secreted into the alveolar space, we analysed the biosynthesis and processing of this precursor in an 'in vitro' system. Our results show that the SP-C precursor is a 21 kDa integral membrane protein. It is anchored in the membrane by a hydrophobic domain that comprises the 20-amino-acid-residues-long hydrophobic core of the mature SP-C peptide. The N-terminus remains in the cytoplasm, which leads to a type II transmembrane orientation of the precursor. Membrane integration occurs in a signal-peptidase-independent manner. The hydrophobic domain acts as both signal sequence and membrane-anchoring domain. We suggest that correct membrane insertion of the SP-C precursor, which is strictly dependent on the hydrophobic-amino-acid sequence represented by the hydrophobic core of the mature SP-C, is itself a prerequisite for further processing and intracellular transport of the mature SP-C.
Keller
A
A
Department of Molecular Biology, Byk Gulden Pharmaceuticals, Konstanz, Federal Republic of Germany.
Eistetter
H R
HR
Voss
T
T
Schäfer
K P
KP
D000818:Animals; D001483:Base Sequence; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000235:genetics; D010450:Endopeptidases / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008861:Microsomes / Q000378:metabolism; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010957:Plasmids; D014176:Protein Biosynthesis; D011498:Protein Precursors / Q000235:genetics*; D011499:Protein Processing, Post-Translational; D011510:Proteolipids / Q000235:genetics* / Q000302:isolation & purification; D011663:Pulmonary Surfactants / Q000235:genetics* / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D015183:Restriction Mapping; D012156:Reticulocytes / Q000378:metabolism; D014158:Transcription, Genetic
D008565:Membrane Proteins; D011498:Protein Precursors; D011510:Proteolipids; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D004247:DNA; D015500:Chloramphenicol O-Acetyltransferase; D010450:Endopeptidases