title: Primary structure differences of human surfactant-associated proteins isolated from normal and proteinosis lung.
abstract: The primary structures of human pulmonary surfactant-associated proteins SP-A, SP-B and SP-C isolated from lung lavage of patients with alveolar proteinosis exhibit significant differences from lung surfactant proteins isolated from lungs of healthy individuals. In contrast to SP-A from normal lungs, proteinosis SP-A was shown by SDS gel electrophoresis to contain large amounts of unreducibly cross-linked beta chains. Specific primary structure modifications of SP-C and SP-B proteins were established by direct molecular weight and structural analysis, using [252Cf]plasma desorption mass spectrometry (PD/MS) as the principal method. In comparison to normal lung surfactant SP-B, proteinosis SP-B showed a significantly increased molecular weight by approx. 500 Da for the unreduced protein dimer. SP-C proteins from normal lungs were identified to possess a bis-cysteinyl-5,6-(thioester)palmitoylated structure, and to contain a frayed N-terminus resulting in two sequences of 34 and 35 amino acid residues. In contrast, SP-C from proteinosis patients was modified by (i) partial or even complete removal of palmitate residues and (ii) additional N-terminal proteolytic degradation. These results indicate the presence of pathophysiological structure modifications, which are likely to occur in the alveolar space, and may lead to a reduced surfactant function.
authors.affiliation: Byk Gulden Pharmaceuticals, Konstanz, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Voss
authors.forename: K P
authors.initials: KP
authors.lastname: Schäfer
authors.forename: P F
authors.initials: PF
authors.lastname: Nielsen
authors.forename: A
authors.initials: A
authors.lastname: Schäfer
authors.forename: C
authors.initials: C
authors.lastname: Maier
authors.forename: E
authors.initials: E
authors.lastname: Hannappel
authors.forename: J
authors.initials: J
authors.lastname: Maassen
authors.forename: B
authors.initials: B
authors.lastname: Landis
authors.forename: K
authors.initials: K
authors.lastname: Klemm
authors.forename: M
authors.initials: M
authors.lastname: Przybylski
mesh_terms: D000595:Amino Acid Sequence; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D006023:Glycoproteins / Q000737:chemistry*; D006801:Humans; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011510:Proteolipids / Q000737:chemistry*; D011649:Pulmonary Alveolar Proteinosis / Q000378:metabolism*; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000737:chemistry*
chemical_list: D006023:Glycoproteins; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants