Structure and Function of Pulmonary Surfactant Proteins

Abstract

Pulmonary surfactant is a lipid/protein complex essential to keep the airspaces of mammalian lungs open. It forms surface‐active films at the respiratory air–liquid interface, reducing surface tension to a minimum and thus minimising the work of breathing. At the same time, surfactant establishes the first barrier against the entry of potential pathogens through the large surface that lungs expose to environment. Both the interfacial and the innate defence activities depend critically on the presence of highly specialised evolutionarily conserved surfactant‐associated proteins. The structure and molecular mechanisms of these proteins have been extensively characterised in the last decades, in studies that constitute the basis for current models on surfactant mechanisms at the alveolar spaces, in health and disease. This article summarises the current knowledge on the structure–function relationships defining the molecular action of pulmonary surfactant proteins and how they are being key actors to maintain operative breathing in the lungs.

Key Concepts

  • The presence of specific proteins is essential for pulmonary surfactant to play its crucial role in stabilising the respiratory air–liquid interface.
  • Collectin proteins SP‐A and SP‐D oligomerise to form trimers and supratrimeric oligomers with multivalent binding capacities to sugars and lipids and participate in innate defence mechanisms, binding to the surface of pathogens and allergens to facilitate their clearance.
  • Surfactant protein SP‐B is essential for life; its absence is associated with an irreversible respiratory failure at birth.
  • SP‐B belongs to the saposin protein family and assembles as ring‐shaped oligomers that enclose hydrophobic channels competent to transfer phospholipids between membranes and between membranes and the interface, avoiding its exposure to aqueous environments.
  • Some synthetic peptides designed to mimic key SP‐B motifs are being used to produce alternative surfactant preparations for therapeutic applications.
  • Protein SP‐C is a very hydrophobic helical protein whose expression is linked to the differentiation of lung tissue. Its oligomerisation is associated with surfactant membrane fragmentation and their interconversions at the alveolar spaces.

Keywords: lung surfactant; surface tension; lipid–protein interactions; membrane proteins, collectin; saposin; air–liquid interface; innate defence

Figure 1. Pulmonary surfactant proteins and their role in formation and stabilisation of interfacial surfactant films. (a) Surfactant multilayered films are stabilised by surfactant proteins SP‐A, SP‐B and SP‐C, while SP‐D is obtained nonassociated with membranes at the bronchoalveolar fluid. (b) Representation of surfactant composition, in which the proportion of the different surfactant‐associated proteins is indicated in detail.
Figure 2. Structure of the proteins from the collectin family. The domain organisation of the collectin proteins is shown in the monomer. The N‐terminal domain containing cysteine residues is followed by the collagenous region and then by the helical coiled–coiled sequence (neck domain) and the C‐terminal carbohydrate recognition domain (CRD). Three monomers oligomerise to form a triple helix over the collagen‐like region and a cluster of three CRDs at the C‐terminal end. Interchain disulfide bonds at the N‐terminal region stabilise the higher oligomeric structure. The collectin CL‐43 is observed as a monomer of the triple helix structure (1 × 3). SP‐A is assembled into octadecamers (8 × 3). MBL is found in a series of oligomers but here is only presented as octadecamer. SP‐D and conglutinin are dodecamers formed by four triple helix subunits (4 × 3). Reproduced with permission from Hansen and Holmskov . © Elsevier.
Figure 3. Lung collectins SP ‐A and SP ‐D. (a) Representation of the primary structure of SP‐A showing its four structural modules: Cysteine‐rich N‐terminal domain, collagenous domain, neck domain and carbohydrate recognition domain (CRD). The crystallography structure represented corresponds to the SP‐A neck domain and the CRD (PDB 1R13). SP‐A assembles progressively from the monomer to the octadecameric structure. (b) Primary structure of SP‐D exhibiting the four structural domains: Cysteine‐rich domain, collagen like domain, neck domain and CRD. The high‐resolution 3D structure represents the SP‐D neck and carbohydrate recognition domains (PDB 1B08). SP‐D assembles from monomer to dodecamer structure.
Figure 4. Structure of surfactant protein SP ‐B. (a) Sequence alignment (Clustal Omega) is shown highlighting different types of residues: aromatic (green), basic (blue), acidic (red), cysteine (yellow) and hydrophobic (grey). The three intramolecular disulfide bonds are also shown. (b) Crystal structure of the saposin NK‐lysin (PDB 1NKL) illustrates the homology with SP‐B monomer. The model for the three‐dimensional structure of SP‐B is based on the structure of Saposin B dimer, assembled in hexameric configuration. Images of SP‐B ring‐shaped oligomers have been taken by EM (c) and AFM (d). (e) Proposed mechanism of action of oligomeric SP‐B complexes. SP‐B rings could interconnect surfactant membranes. Each SP‐B dimer could accommodate a phospholipid molecule into its hydrophobic cavity. The cartoon represents how the whole SP‐B oligomer could promote intermembrane phospholipid flows.
Figure 5. Post‐translational maturation o f proSP ‐B and proSP ‐C in type II pneumocytes. Both SP‐B and SP‐C are synthesised as large precursors, proSP‐B and proSP‐C, which are sequentially cleaved along the exocytosis pathway (ER, endoplasmic reticulum; MVB, multivesicular bodies; CB, composite bodies; LB, lamellar bodies) until they are assembled as lipid/protein complexes into lamellar bodies for their secretion. ?, Cleavage step promoted by a yet unknown protease.
Figure 6. Synthetic SP ‐B analogues used in the development of synthetic surfactants. Mini‐B sequence has been designed to mimic N‐terminal and C‐terminal helical segments of SP‐B (PDB 2DWF). The surfactant peptide KL4 sequence mimics sequence amphipathic patterns of helical segments in SP‐B.
Figure 7. Structure, sequence and oligomerisation‐promoted membrane perturbation of surfactant protein SP ‐C. (a) The helical structure of porcine SP‐C was determined by NMR in organic solvent (PDB 1SPF, without displaying the palmitoyl chains). The SP‐C sequence alignment (Clustal Omega) is shown highlighting the most conserved residues (*), cysteines at the palmitoylation site (pink) and positively charged amino acids (blue) at physiological pH. (b) The model illustrates the potential mechanism of membrane curvature induced by SP‐C in lipid bilayers.
Figure 8. proSP ‐C and the BRICHOS domain. (a) The sequence of proSP‐C is shown with the residues included into the intramolecular chaperone domain BRICHOS highlighted. (b) Crystal structure of the BRICHOS domain.
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References

Akinbi HT , Breslin JS , Ikegami M , et al. (1997) Rescue of SP‐B knockout mice with a truncated SP‐B proprotein. Function of the C‐terminal propeptide. Journal of Biological Chemistry 272 (15): 9640–9647.

Ariki S , Kojima T , Gasa S , et al. (2011) Pulmonary collectins play distinct roles in host defense against Mycobacterium avium . Journal of Immunology 187 (5): 2586–2594.

Arroyo R , Martin‐Gonzalez A , Echaide M , et al. (2018) Supramolecular assembly of human pulmonary surfactant protein SP‐D. Journal of Molecular Biology 430 (10): 1495–1509.

Baatz JE , Smyth KL , Whitsett JA , et al. (1992) Structure and functions of a dimeric form of surfactant protein SP‐C: a Fourier transform infrared and surfactometry study. Chemistry and Physics of Lipids 63 (1–2): 91–104.

Baumgart F , Ospina OL , Mingarro I , et al. (2010) Palmitoylation of pulmonary surfactant protein SP‐C is critical for its functional cooperation with SP‐B to sustain compression/expansion dynamics in cholesterol‐containing surfactant films. Biophysical Journal 99: 3234–3243.

Bernardino de la Serna J , Vargas R , Picardi V , et al. (2013) Segregated ordered lipid phases and protein‐promoted membrane cohesivity are required for pulmonary surfactant films to stabilize and protect the respiratory surface. Faraday Discussions 161: 535–589.

Blanco O and Perez‐Gil J (2007) Biochemical and pharmacological differences between preparations of exogenous natural surfactant used to treat Respiratory Distress Syndrome: role of the different components in an efficient pulmonary surfactant. European Journal of Pharmacology 568 (1–3): 1–15.

Bridges JP , Wert SE , Nogee LM , et al. (2003) Expression of a human surfactant protein C mutation associated with interstitial lung disease disrupts lung development in transgenic mice. Journal of Biological Chemistry 278 (52): 52739–52746.

Cabre EJ , Martinez‐Calle M , Prieto M , et al. (2018) Homo‐ and hetero‐oligomerization of hydrophobic pulmonary surfactant proteins SP‐B and SP‐C in surfactant phospholipid membranes. Journal of Biological Chemistry 293 (24): 9399–9411.

Clark JC , Wert SE , Bachurski CJ , et al. (1995) Targeted disruption of the surfactant protein B gene disrupts surfactant homeostasis, causing respiratory failure in newborn mice. Proceedings of the National Academy of Sciences of the United States of America 92: 7794–7798.

Cockshutt AM , Weitz J and Possmayer F (1990) Pulmonary surfactant‐associated protein A enhances the surface activity of lipid extract surfactant and reverses inhibition by blood proteins in vitro. Biochemistry 29 (36): 8424–8429.

Cochrane CG and Revak SD (1991) Pulmonary surfactant protein B (SP‐B): structure‐function relationships. Science 254 (5031): 566–568.

Crouch E , Persson A , Chang D , et al. (1994) Molecular structure of pulmonary surfactant protein D (SP‐D). Journal of Biological Chemistry 269 (25): 17311–17319.

Crouch EC (2000) Surfactant protein‐D and pulmonary host defense. Respiratory Research 1 (2): 93–108.

Crouch E , Hartshorn K and Ofek I (2000) Collectins and pulmonary innate immunity. Immunological Reviews 173: 52–65.

Crouch E and Wright JR (2001) Surfactant proteins A and D and pulmonary host defense. Annual Review of Physiology 63: 521–554.

Curstedt T and Johansson J (2010) Different effects of surfactant proteins B and C ‐ implications for development of synthetic surfactants. Neonatology 97 (4): 367–372.

Dluhy RA , Shanmukh S , Leapard JB , et al. (2003) Deacylated pulmonary surfactant protein SP‐C transforms from alpha‐helical to amyloid fibril structure via a pH‐dependent mechanism: an infrared structural investigation. Biophysical Journal 85: 2417–2429.

Echaide M , Autilio C , Arroyo R , et al. (2017) Restoring pulmonary surfactant membranes and films at the respiratory surface. Biochimica et Biophysica Acta, Biomembranes 1859 (9 Pt B): 1725–1739.

van Eijk M , Rynkiewicz MJ , White MR , et al. (2012) A unique sugar‐binding site mediates the distinct anti‐influenza activity of pig surfactant protein D. Journal of Biological Chemistry 287 (32): 26666–26677.

Floros J and Hoover RR (1998) Genetics of the hydrophilic surfactant proteins A and D. Biochimica et Biophysica Acta 1408 (2–3): 312–322.

Floros J , Wang G and Mikerov AN (2009) Genetic complexity of the human innate host defense molecules, surfactant protein A1 (SP‐A1) and SP‐A2‐‐impact on function. Critical Reviews in Eukaryotic Gene Expression 19 (2): 125–137.

Gao E , Wang Y , McCormick SM , et al. (1996) Characterization of two baboon surfactant protein A genes. The American Journal of Physiology 271 (4 Pt 1): L617–L630.

Garcia‐Verdugo I , Wang G , Floros J , et al. (2002) Structural analysis and lipid‐binding properties of recombinant human surfactant protein a derived from one or both genes. Biochemistry 41 (47): 14041–14053.

Glenner GG (1980) Amyloid deposits and amyloidosis. The beta‐fibrilloses (first of two parts). The New England Journal of Medicine 302 (23): 1283–1292.

Gómez‐Gil L , Pérez‐Gil J and Goormaghtigh E (2009a) Cholesterol modulates the exposure and orientation of pulmonary surfactant protein SP‐C in model surfactant membranes. Biochimica et Biophysica Acta ‐ Biomembranes 1788 (9): 1907–1915.

Gómez‐Gil L , Schürch D , Goormaghtigh E , et al. (2009b) Pulmonary surfactant protein SP‐C counteracts the deleterious effects of cholesterol on the activity of surfactant films under physiologically relevant compression‐expansion dynamics. Biophysical Journal 97 (10): 2736–2745.

Guttentag SH , Beers MF , Bieler BM , et al. (1998) Surfactant protein B processing in human fetal lung. The American Journal of Physiology 275 (3 Pt 1): L559–L566.

Haagsman HP , White RT , Schilling J , et al. (1989) Studies of the structure of lung surfactant protein SP‐A. The American Journal of Physiology 257 (6 Pt 1): L421–L429.

Søren Hansen , Uffe Holmskov (1998) Structural aspects of collectins and receptors for collectins, Immunobiology, 199(2): 165–189. DOI: 10.1016/S0171‐2985(98)80025‐9.

Holmskov U , Malhotra R , Sim RB , et al. (1994) Collectins: collagenous C‐type lectins of the innate immune defense system. Immunology Today 15 (2): 67–74.

Hoppe HJ and Reid KB (1994) Trimeric C‐type lectin domains in host defence. Structure 2 (12): 1129–1133.

Johansson J , Curstedt T and Joernvall H (1991) Surfactant protein B: disulfide bridges, structural properties and kringle similarities. Biochemistry 30 (28): 6917–6921.

Johansson J , Szyperski T , Curstedt T , et al. (1994) The NMR structure of the pulmonary surfactant‐associated polypeptide SP‐C in an apolar solvent contains a valyl‐rich alpha‐helix. Biochemistry 33: 6015–6023.

Johansson J (1998) Structure and properties of surfactant protein C. Biochimica et Biophysica Acta 1408: 161–172.

Johansson J (2003) Molecular determinants for amyloid fibril formation: lessons from lung surfactant protein C. Swiss Medical Weekly 133 (19–20): 275–282.

Johansson H , Nerelius C , Nordling K , et al. (2009) Preventing amyloid formation by catching unfolded transmembrane segments. Journal of Molecular Biology 389 (2): 227–229.

Kairys V , Gilson MK and Luy B (2004) Structural model for an AxxxG‐mediated dimer of surfactant‐associated protein C. European Journal of Biochemistry 271 (11): 2086–2092.

Lopez‐Rodriguez E and Perez‐Gil J (2014) Structure‐function relationships in pulmonary surfactant membranes: from biophysics to therapy. Biochimica et Biophysica Acta 1838 (6): 1568–1585.

Lopez‐Rodriguez E , Pascual A , Arroyo R , et al. (2016) Human pulmonary surfactant protein SP‐A1 provides maximal efficiency of lung interfacial films. Biophysical Journal 111 (3): 524–536.

Lukovic D , Plasencia I , Taberner FJ , et al. (2006) Production and characterisation of recombinant forms of human pulmonary surfactant protein C (SP‐C): structure and surface activity. Biochimica et Biophysica Acta 1758 (4): 509–518.

Lukovic D , Cruz A , Gonzalez‐Horta A , et al. (2012) Interfacial behavior of recombinant forms of human pulmonary surfactant protein SP‐C. Langmuir 28 (20): 7811–7825.

Mahajan L , Gautam P , Dodagatta‐Marri E , et al. (2014) Surfactant protein SP‐D modulates activity of immune cells: proteomic profiling of its interaction with eosinophilic cells. Expert Review of Proteomics 11 (3): 355–369.

McCormack FX , Damodarasamy M and Elhalwagi BM (1999) Deletion mapping of N‐terminal domains of surfactant protein A. The N‐terminal segment is required for phospholipid aggregation and specific inhibition of surfactant secretion. Journal of Biological Chemistry 274 (5): 3173–3181.

McMahon HT and Gallop JL (2005) Membrane curvature and mechanisms of dynamic cell membrane remodelling. Nature 438 (7068): 590–596.

Mingarro I , Lukovic D , Vilar M , et al. (2008) Synthetic pulmonary surfactant preparations: new developments and future trends. Current Medicinal Chemistry 15 (4): 393–403.

Nerelius C , Martin E , Peng S , et al. (2008) Mutations linked to interstitial lung disease can abrogate anti‐amyloid function of prosurfactant protein C. The Biochemical Journal 416 (2): 201–209.

Nerelius C , Gustafsson M , Nordling K , et al. (2009) Anti‐amyloid activity of the C‐terminal domain of proSP‐C against amyloid beta‐peptide and medin. Biochemistry 48 (17): 3778–3786.

Ogasawara Y , Kuroki Y and Akino T (1992) Pulmonary surfactant protein D specifically binds to phosphatidylinositol. Journal of Biological Chemistry 267 (29): 21244–21249.

Ogihara NL , Weiss MS , Degrado WF , et al. (1997) The crystal structure of the designed trimeric coiled coil coil‐VaLd: implications for engineering crystals and supramolecular assemblies. Protein Science 6 (1): 80–88.

Olmeda B , Garcia‐Alvarez B and Perez‐Gil J (2013) Structure‐function correlations of pulmonary surfactant protein SP‐B and the saposin‐like family of proteins. European Biophysics Journal 42 (2–3): 209–222.

Olmeda B , Garcia‐Alvarez B , Gomez MJ , et al. (2015) A model for the structure and mechanism of action of pulmonary surfactant protein B. The FASEB Journal 29 (10): 4236–4247.

Pastva AM , Wright JR and Williams KL (2007) Immunomodulatory roles of surfactant proteins A and D: implications in lung disease. Proceedings of the American Thoracic Society 4 (3): 252–257.

Peng S , Fitzen M , Jornvall H , et al. (2010) The extracellular domain of Bri2 (ITM2B) binds the ABri peptide (1–23) and amyloid beta‐peptide (Abeta1‐40): Implications for Bri2 effects on processing of amyloid precursor protein and Abeta aggregation. Biochemical and Biophysical Research Communications 393 (3): 356–361.

Pérez‐Gil J (2008) Structure of pulmonary surfactant membranes and films: the role of proteins and lipid‐protein interactions. Biochimica et Biophysica Acta 1778: 1676–1695.

Pérez‐Gil J (2010) El sistema surfactante pulmonar. Investigación y ciencia 401: 28–45.

Perez‐Gil J and Weaver TE (2010) Pulmonary surfactant pathophysiology: current models and open questions. Physiology (Bethesda) 25: 132–141.

Persson A , Chang D , Rust K , et al. (1989) Purification and biochemical characterization of CP4 (SP‐D), a collagenous surfactant‐associated protein. Biochemistry 28 (15): 6361–6367.

Plasencia I , Rivas L , Keough KM , Marsh D and Pérez‐Gil J (2004) The N‐terminal segment of pulmonary surfactant lipopeptide SP‐C has intrinsic propensity to interact with and perturb phospholipid bilayers. The Biochemical Journal 377: 183–193.

Possmayer F (1988) A proposed nomenclature for pulmonary surfactant‐associated proteins. The American Review of Respiratory Disease 138 (4): 990–998.

Rochet JC and Lansbury PT Jr (2000) Amyloid fibrillogenesis: themes and variations. Current Opinion in Structural Biology 10 (1): 60–68.

Roldan N , Goormaghtigh E , Pérez‐Gil J , et al. (2015) Palmitoylation as a key factor to modulate SP‐C‐lipid interactions in lung surfactant membrane multilayers. Biochimica et Biophysica Acta ‐ Biomembranes 1848 (1): 184–191.

Roldan N , Nyholm TKM , Slotte JP , et al. (2016) Effect of lung surfactant protein SP‐C and SP‐C‐promoted membrane fragmentation on cholesterol dynamics. Biophysical Journal 111 (8): 1703–1713.

Ryan MA , Qi X , Serrano AG , et al. (2005) Mapping and analysis of the lytic and fusogenic domains of surfactant protein B. Biochemistry 44 (3): 861–872.

Salgado D , Fischer R , Schillberg S , et al. (2014) Comparative evaluation of heterologous production systems for recombinant pulmonary surfactant protein D. Frontiers in Immunology 5: 623.

Sanchez‐Pulido L , Devos D and Valencia A (2002) BRICHOS: a conserved domain in proteins associated with dementia, respiratory distress and cancer. Trends in Biochemical Sciences 27 (7): 329–332.

Sarker M , Waring AJ , Walther FJ , et al. (2007) Structure of mini‐B, a functional fragment of surfactant protein B, in detergent micelles. Biochemistry 46 (39): 11047–11056.

Schürch D , Ospina OL , Cruz A , et al. (2010) Combined and independent action of proteins SP‐B and SP‐C in the surface behavior and mechanical stability of pulmonary surfactant films. Biophysical Journal 99 (10): 3290–3299.

Shrive AK , Martin C , Burns I , et al. (2009) Structural characterisation of ligand‐binding determinants in human lung surfactant protein D: influence of Asp325. Journal of Molecular Biology 394 (4): 776–788.

Spragg RG , Taut FJH , Gunther A , et al. (2009) Surfactant replacement therapy in ARDS. Chest 136 (1): 321–322.

Strang CJ , Slayter HS , Lachmann PJ , et al. (1986) Ultrastructure and composition of bovine conglutinin. The Biochemical Journal 234 (2): 381–389.

Szyperski T , Vandenbussche G , Curstedt T , et al. (1998) Pulmonary surfactant‐associated polypeptide C in a mixed organic solvent transforms from a monomeric alpha‐helical state into insoluble beta‐sheet aggregates. Protein Science 7: 2533–2540.

Ten Brinke A , Batenburg JJ , Haagsman HP , et al. (2002) Differential effect of brefeldin A on the palmitoylation of surfactant protein C proprotein mutants. Biochemical and Biophysical Research Communications 290 (1): 532–538.

Vandenbussche G , Clercx A , Clercx M , et al. (1992) Secondary structure and orientation of the surfactant protein SP‐B in a lipid environment. A Fourier transform infrared spectroscopy study. Biochemistry 31 (38): 9169–9176.

Voss T , Eistetter H , Schafer KP , et al. (1988) Macromolecular organization of natural and recombinant lung surfactant protein SP 28–36. Structural homology with the complement factor C1q. Journal of Molecular Biology 201 (1): 219–227.

Voss T , Melchers K , Scheirle G , et al. (1991) Structural comparison of recombinant pulmonary surfactant protein SP‐A derived from two human coding sequences: implications for the chain composition of natural human SP‐A. American Journal of Respiratory Cell and Molecular Biology 4 (1): 88–94.

Walther FJ , Waring AJ , Sherman MA , et al. (2007) Hydrophobic surfactant proteins and their analogues. Neonatology 91 (4): 303–310.

Walther FJ , Gordon LM and Waring AJ (2016) Design of surfactant protein B peptide mimics based on the saposin fold for synthetic lung surfactants. Biomedicine Hub 1 (3): 451076.

Weaver TE and Conkright JJ (2001) Function of surfactant proteins B and C. Annual Review of Physiology 63: 555–578.

Weaver TE , Na CL and Stahlman M (2002) Biogenesis of lamellar bodies, lysosome‐related organelles involved in storage and secretion of pulmonary surfactant. Seminars in Cell & Developmental Biology 13 (4): 263–270.

Wert SE , Whitsett JA and Nogee LM (2009) Genetic disorders of surfactant dysfunction. Pediatric and Developmental Pathology 12 (4): 253–274.

White RT , Damm D , Miller J , et al. (1985) Isolation and characterization of the human pulmonary surfactant apoprotein gene. Nature 317 (6035): 361–363.

Willander H , Askarieh G , Landreh M , et al. (2012) High‐resolution structure of a BRICHOS domain and its implications for anti‐amyloid chaperone activity on lung surfactant protein C. Proceedings of the National Academy of Sciences of the United States of America 109 (7): 2325–2329.

Wright JR (2005) Immunoregulatory functions of surfactant proteins. Nature Reviews. Immunology 5 (1): 58–68.

Wustneck N , Wustneck R , Perez‐Gil J , et al. (2003) Effects of oligomerization and secondary structure on the surface behavior of pulmonary surfactant proteins SP‐B and SP‐C. Biophysical Journal 84 (3): 1940–1949.

Yang L , Johansson J , Ridsdale R , et al. (2010) Surfactant protein B propeptide contains a saposin‐like protein domain with antimicrobial activity at low pH. Journal of Immunology 184 (2): 975–983.

Further Reading

Bernhard W (2016) Lung surfactant: Function and composition in the context of development and respiratory physiology. Annals of Anatomy 208: 146–150.

Guagliardo R , Pérez‐Gil J , De Smedt S , et al (2018) Pulmonary surfactant and drug delivery: focusing on the role of surfactant proteins. Journal of Controlled Release 291: 116–126.

Han S and Mallampalli RK (2015) The role of surfactant in lung disease and host defense against pulmonary infections. Annals of the American Thoracic Society 12 (5): 765–774.

Ketko AK and Donn SM (2014) Surfactant‐associated proteins: structure, function and clinical implications. Current Pediatric Reviews 10 (2): 162–167.

Olmeda B , Martínez‐Calle M and Pérez‐Gil J (2017) Pulmonary surfactant metabolism in the alveolar airspace: biogenesis, extracellular conversions, recycling. Annals of Anatomy 209: 78–92.

Orgeig S , Morrison JL and Daniels CB (2015) Evolution, development, and function of the pulmonary surfactant system in normal and perturbed environments. Comprehensive Physiology 6 (1): 363–422.

Parra E and Pérez‐Gil J (2015) Composition, structure and mechanical properties define performance of pulmonary surfactant membranes and films. Chemistry and Physics of Lipids 185: 153–175.

Sunde M , Pham CLL and Kwan AH (2017) Molecular characteristics and biological functions of surface‐active and surfactant proteins. Annual Review of Biochemistry 86: 585–608.

Whitsett JA , Wert SE and Weaver TE (2015) Diseases of pulmonary surfactant homeostasis. Annual Review of Pathology 10: 371–393.

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García‐Álvarez, Begoña, Alonso, Alejandro, and Pérez‐Gil, Jesús(Feb 2019) Structure and Function of Pulmonary Surfactant Proteins. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0027639]