Structural highlights
Disease
PSPB_HUMAN Defects in SFTPB are the cause of pulmonary surfactant metabolism dysfunction type 1 (SMDP1) [MIM:265120; also called pulmonary alveolar proteinosis due to surfactant protein B deficiency. A rare lung disorder due to impaired surfactant homeostasis. It is characterized by alveolar filling with floccular material that stains positive using the periodic acid-Schiff method and is derived from surfactant phospholipids and protein components. Excessive lipoproteins accumulation in the alveoli results in severe respiratory distress.[1] Genetic variations in SFTPB are a cause of susceptibility to respiratory distress syndrome in premature infants (RDS) [MIM:267450. RDS is a lung disease affecting usually premature newborn infants. It is characterized by deficient gas exchange, diffuse atelectasis, high-permeability lung edema and fibrin-rich alveolar deposits called 'hyaline membranes'. Note=A variation Ile to Thr at position 131 influences the association between specific alleles of SFTPA1 and respiratory distress syndrome in premature infants.[2]
Function
PSPB_HUMAN Pulmonary surfactant-associated proteins promote alveolar stability by lowering the surface tension at the air-liquid interface in the peripheral air spaces. SP-B increases the collapse pressure of palmitic acid to nearly 70 millinewtons per meter.
Publication Abstract from PubMed
Surfactant protein B (SP-B) is essential for normal lung surfactant function. Theoretical models predict that the disulfide cross-linked, N- and C-terminal domains of SP-B fold as charged amphipathic helices, and suggest that these adjacent helices participate in critical surfactant activities. This hypothesis is tested using a disulfide-linked construct (Mini-B) based on the primary sequences of the N- and C-terminal domains. Consistent with theoretical predictions of the full-length protein, both isotope-enhanced Fourier transform infrared (FTIR) spectroscopy and molecular modeling confirm the presence of charged amphipathic alpha-helices in Mini-B. Similar to that observed with native SP-B, Mini-B in model surfactant lipid mixtures exhibits marked in vitro activity, with spread films showing near-zero minimum surface tensions during cycling using captive bubble surfactometry. In vivo, Mini-B shows oxygenation and dynamic compliance that compare favorably with that of full-length SP-B. Mini-B variants (i.e. reduced disulfides or cationic residues replaced by uncharged residues) or Mini-B fragments (i.e. unlinked N- and C-terminal domains) produced greatly attenuated in vivo and in vitro surfactant properties. Hence, the combination of structure and charge for the amphipathic alpha-helical N- and C-terminal domains are key to SP-B function.
The role of charged amphipathic helices in the structure and function of surfactant protein B.,Waring AJ, Walther FJ, Gordon LM, Hernandez-Juviel JM, Hong T, Sherman MA, Alonso C, Alig T, Braun A, Bacon D, Zasadzinski JA J Pept Res. 2005 Dec;66(6):364-74. PMID:16316452[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ballard PL, Nogee LM, Beers MF, Ballard RA, Planer BC, Polk L, deMello DE, Moxley MA, Longmore WJ. Partial deficiency of surfactant protein B in an infant with chronic lung disease. Pediatrics. 1995 Dec;96(6):1046-52. PMID:7491219
- ↑ Haataja R, Ramet M, Marttila R, Hallman M. Surfactant proteins A and B as interactive genetic determinants of neonatal respiratory distress syndrome. Hum Mol Genet. 2000 Nov 1;9(18):2751-60. PMID:11063734
- ↑ Waring AJ, Walther FJ, Gordon LM, Hernandez-Juviel JM, Hong T, Sherman MA, Alonso C, Alig T, Braun A, Bacon D, Zasadzinski JA. The role of charged amphipathic helices in the structure and function of surfactant protein B. J Pept Res. 2005 Dec;66(6):364-74. PMID:16316452 doi:http://dx.doi.org/JPP300
