Isolation and characterization of the human pulmonary surfactant apoprotein gene

Abstract

Pulmonary surfactant is a phospholipid-protein complex which serves to lower the surface tension at the air-liquid interface in the alveoli of the mammalian lung and is essential for normal respiration. Inadequate levels of surfactant at birth, a frequent situation in premature infants, results in respiratory failure. In all species examined, surfactant is composed primarily of dipalmitoylphosphatidylcholine and two major protein species of relative molecular mass (Mr) 32,000 (32K) and 10K (refs 2-5). Reconstitution in vitro of purified 32K pulmonary surfactant apoprotein (PSAP) with synthetic lipids forms a lipoprotein complex that lowers surface tension by spreading to create a thin interfacial film. Here we describe the cloning of the human PSAP gene and complementary DNA, and discuss features of the unusual encoded protein.

Collectins — soluble proteins containing collagenous regions and lectin domains — and their roles in innate immunity

“…Therefore, although the requirement for hydroxyl-groups of the mannose-or galactose-type within the binding-site on the carbohydrate molecules is determined by the E-N/Q-D pair of residues, other differences seen in the sequences of the lectin domains, and of the extensive loop carrying the binding sites in particular, seem to be also involved in ligand selection in the in vivo interaction of C-type lectins with complex carbohydrate structures. Domains identified by sequence comparison and predicted to have an overall folding similar to that seen in the crystal structure of the C-type lectin domain of MBP (Weis et al, 1991b), but lacking some of the characteristic residues involved in calcium/carbohydrate binding, are seen in a number of type I1 membrane proteins ( QPD-E-WND gal Tanaka et al, 1988 QPD-E-WND gal Zimmerman & Ruoslahti, 1989 QPD-E-WND gal Drickamer, 1981Spiess & Lodish, 1985Drickamer et al, 1984Ii et al, 1990Hoyle & Hill, 1991Sat0 et al, 1992Curtis et al, 1992Suter et al, 1987Yokoyama et al, 1989Chan & Takei, 1989Giorda et al, 1990Van Hoegen et al, 1990Houchins et al, 1991Wong et al, 1991Yoshimatsu et al, 1992Lee et al, 1991Taylor et al, 1989Drickamer et al, 1986White et al, 1985Benson et al, 1985Rust et al, 1991Holmskov et al, 1993bHolmskov et al, 1993aLasky et al, 1989Bevilacqua et al, 1991Johnson et al, 1989Christa et al, 1994Ng & Hew, 1992Ewart et al, 1992Rouquier et al, 1991Taylor et al, 1990 EPN-E-WND man (Drickamer, 1992). Not all of the carbohydrate specificities have been determined (*), and certain proteins, although a Proteins containing C-type lectin domains or regions w...…”

“…The human MBP gene (Fig. 4) is 7 kb long and contains 4 exons: exon 1 encodes the leader peptide, N-terminal region and part of the collagen-like region; exon 2 encodes the remainder of the collagen-like region; and exon 3 encodes the sequences White et al, 1985;Floros et al, 1986;Katyal et al, 1992). The human SP-A structural gene (gene symbol SFTP 1) is 4.5 kb long and contains 5 exons, with exon 2 encoding the signal peptide, the amino-terminal region, and the first 10 Gly-Xaa-Yaa triplets, and exon 3 encoding the remaining 13 Gly-Xaa-Yaa triplets.…”

“…Exon 4 and part of exon 5 encode a putative amphipathic a-helical region, whereas the remainder of exon 5 encodes the C-type lectin domain. The 2 SP-A genes that are expressed encode for polypeptides differing at only 6 amino acid positions (White et al, 1985;Katyal et al, 1992). SP-A has been cloned at the cDNA level in a variety of other species, such as dog, rabbit, rat, and mouse (Korfhagen et al, 1991).…”

Glucocorticoid inhibition of human SP-A1 promoter activity in NCI-H441 cells

“…Human SP-A is encoded by two very similar but non-identical genes, SP-A1 [4] and SP-A2 [5]. The two genes are 94 % identical at the nucleotide level and encode proteins with about 96 % identity.…”

Effect of canine surfactant protein (SP‐A) on the respiratory burst of phagocytic cells

“…SP-A can bind lipids [4] and mannose in a lectin-like manner [5]. Amino acid sequences from human [6,7] and dog SP-A [8] revealed a collagenlike region within the NHz-terminal half and a globular region within the COOH-terminal half of the polypeptide chain. Analysis of the macromolecular organization proved that SP-A aggregates to a complex of 18 polypeptides with 6 collagen-triple helices [9,10], and that this structure is highly homologous to the hexameric structure of Clq [9], a subcomponent of the first component of the classical complement pathway.…”