European Biophysics Journal

, Volume 42, Issue 2–3, pp 209–222

Structure–function correlations of pulmonary surfactant protein SP-B and the saposin-like family of proteins

  • Bárbara Olmeda
  • Begoña García-Álvarez
  • Jesús Pérez-Gil
Review

Abstract

Pulmonary surfactant is a lipid-protein complex secreted by the respiratory epithelium of mammalian lungs, which plays an essential role in stabilising the alveolar surface and so reducing the work of breathing. The surfactant protein SP-B is part of this complex, and is strictly required for the assembly of pulmonary surfactant and its extracellular development to form stable surface-active films at the air–liquid alveolar interface, making the lack of SP-B incompatible with life. In spite of its physiological importance, a model for the structure and the mechanism of action of SP-B is still needed. The sequence of SP-B is homologous to that of the saposin-like family of proteins, which are membrane-interacting polypeptides with apparently diverging activities, from the co-lipase action of saposins to facilitate the degradation of sphingolipids in the lysosomes to the cytolytic actions of some antibiotic proteins, such as NK-lysin and granulysin or the amoebapore of Entamoeba histolytica. Numerous studies on the interactions of these proteins with membranes have still not explained how a similar sequence and a potentially related fold can sustain such apparently different activities. In the present review, we have summarised the most relevant features of the structure, lipid-protein and protein–protein interactions of SP-B and the saposin-like family of proteins, as a basis to propose an integrated model and a common mechanistic framework of the apparent functional versatility of the saposin fold.

Keywords

Pulmonary surfactant Saposin Amphipathic helices Surface tension Air–liquid interface Lipid-protein interactions 

References

  1. Ahn VE, Faull KF, Whitelegge JP, Fluharty AL, Prive GG (2003) Crystal structure of saposin B reveals a dimeric shell for lipid binding. Proc Natl Acad Sci USA 100:38–43PubMedCrossRefGoogle Scholar
  2. Ahn VE, Leyko P, Alattia JR, Chen L, Prive GG (2006) Crystal structures of saposins A and C. Protein Sci 15:1849–1857PubMedCrossRefGoogle Scholar
  3. Anderson DH, Sawaya MR, Cascio D, Ernst W, Modlin R, Krensky A, Eisenberg D (2003) Granulysin crystal structure and a structure-derived lytic mechanism. J Mol Biol 325:355–365PubMedCrossRefGoogle Scholar
  4. Andersson M, Curstedt T, Jornvall H, Johansson J (1995) An amphipathic helical motif common to tumourolytic polypeptide NK-lysin and pulmonary surfactant polypeptide SP-B. FEBS Lett 362:328–332PubMedCrossRefGoogle Scholar
  5. Ariki S, Kojima T, Gasa S, Saito A, Nishitani C, Takahashi M, Shimizu T, Kurimura Y, Sawada N, Fujii N, Kuroki Y (2011) Pulmonary collectins play distinct roles in host defense against Mycobacterium avium. J Immunol 187:2586–2594PubMedCrossRefGoogle Scholar
  6. Baatz JE, Elledge B, Whitsett JA (1990) Surfactant protein SP-B induces ordering at the surface of model membrane bilayers. Biochemistry 29:6714–6720PubMedCrossRefGoogle Scholar
  7. Baatz JE, Zou Y, Cox JT, Wang Z, Notter RH (2001) High-yield purification of lung surfactant proteins sp-b and sp-c and the effects on surface activity. Protein Expr Purif 23:180–190PubMedCrossRefGoogle Scholar
  8. Baker NA, Sept D, Joseph S, Holst MJ, McCammon JA (2001) Electrostatics of nanosystems: application to microtubules and the ribosome. Proc Natl Acad Sci USA 98:10037–10041PubMedCrossRefGoogle Scholar
  9. Banares-Hidalgo A, Bolanos-Gutierrez A, Gil F, Cabre EJ, Perez-Gil J, Estrada P (2008) Self-aggregation of a recombinant form of the propeptide NH2-terminal of the precursor of pulmonary surfactant protein SP-B: a conformational study. J Ind Microbiol Biotechnol 35:1367–1376PubMedCrossRefGoogle Scholar
  10. Baoukina S, Tieleman DP (2010) Direct simulation of protein-mediated vesicle fusion: lung surfactant protein B. Biophys J 99:2134–2142PubMedCrossRefGoogle Scholar
  11. Beck DC, Ikegami M, Na CL, Zaltash S, Johansson J, Whitsett JA, Weaver TE (2000) The role of homodimers in surfactant protein B function in vivo. J Biol Chem 275:3365–3370PubMedCrossRefGoogle Scholar
  12. Bernardino de la Serna J, Vargas R, Picardi MV, Cruz A, Arranz R, Valpuesta JM, Mateu L, Perez-Gil J (2012) Segregated ordered lipid phases and protein-promoted membrane cohesivity are required for pulmonary surfactant films to stabilize and protect the respiratory surface. Faraday Disc. doi:10.1039/C2FD20096A
  13. Blanco O, 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. Eur J Pharmacol 568:1–15PubMedCrossRefGoogle Scholar
  14. Brasch F, Johnen G, Winn-Brasch A, Guttentag SH, Schmiedl A, Kapp N, Suzuki Y, Muller KM, Richter J, Hawgood S, Ochs M (2004) Surfactant protein B in type II pneumocytes and intra-alveolar surfactant forms of human lungs. Am J Respir Cell Mol Biol 30:449–458PubMedCrossRefGoogle Scholar
  15. Bruhn H (2005) A short guided tour through functional and structural features of saposin-like proteins. Biochem J 389:249–257PubMedCrossRefGoogle Scholar
  16. Bruhn H, Riekens B, Berninghausen O, Leippe M (2003) Amoebapores and NK-lysin, members of a class of structurally distinct antimicrobial and cytolytic peptides from protozoa and mammals: a comparative functional analysis. Biochem J 375:737–744PubMedCrossRefGoogle Scholar
  17. Bryksa BC, Bhaumik P, Magracheva E, De Moura DC, Kurylowicz M, Zdanov A, Dutcher JR, Wlodawer A, Yada RY (2011) Structure and mechanism of the saposin-like domain of a plant aspartic protease. J Biol Chem 286:28265–28275PubMedCrossRefGoogle Scholar
  18. Bunger H, Kruger RP, Pietschmann S, Wustneck N, Kaufner L, Tschiersch R, Pison U (2001) Two hydrophobic protein fractions of ovine pulmonary surfactant: isolation, characterization, and biophysical activity. Protein Expr Purif 23:319–327PubMedCrossRefGoogle Scholar
  19. Cabre EJ, Malmstrom J, Sutherland D, Perez-Gil J, Otzen DE (2009) Surfactant protein SP-B strongly modifies surface collapse of phospholipid vesicles: insights from a quartz crystal microbalance with dissipation. Biophys J 97:768–776PubMedCrossRefGoogle Scholar
  20. Cabre EJ, Loura LM, Fedorov A, Perez-Gil J, Prieto M (2012) Topology and lipid selectivity of pulmonary surfactant protein SP-B in membranes: answers from fluorescence. Biochim Biophys Acta 1818:1717–1725PubMedCrossRefGoogle Scholar
  21. Chang R, Nir S, Poulain FR (1998) Analysis of binding and membrane destabilization of phospholipid membranes by surfactant apoprotein B. Biochim Biophys Acta 1371:254–264PubMedCrossRefGoogle Scholar
  22. Chavarha M, Khoojinian H, Schulwitz LE Jr, Biswas SC, Rananavare SB, Hall SB (2010) Hydrophobic surfactant proteins induce a phosphatidylethanolamine to form cubic phases. Biophys J 98:1549–1557PubMedCrossRefGoogle Scholar
  23. Clark JC, Wert SE, Bachurski CJ, Stahlman MT, Stripp BR, Weaver TE, Whitsett JA (1995) Targeted disruption of the surfactant protein B gene disrupts surfactant homeostasis, causing respiratory failure in newborn mice. Proc Natl Acad Sci USA 92:7794–7798PubMedCrossRefGoogle Scholar
  24. Cruz A, Casals C, Keough KM, Perez-Gil J (1997) Different modes of interaction of pulmonary surfactant protein SP-B in phosphatidylcholine bilayers. Biochem J 327(Pt 1):133–138PubMedGoogle Scholar
  25. Cruz A, Casals C, Plasencia I, Marsh D, Perez-Gil J (1998) Depth profiles of pulmonary surfactant protein B in phosphatidylcholine bilayers, studied by fluorescence and electron spin resonance spectroscopy. Biochemistry 37:9488–9496PubMedCrossRefGoogle Scholar
  26. Cruz A, Worthman LA, Serrano AG, Casals C, Keough KM, Perez-Gil J (2000) Microstructure and dynamic surface properties of surfactant protein SP-B/dipalmitoylphosphatidylcholine interfacial films spread from lipid-protein bilayers. Eur Biophys J 29:204–213PubMedCrossRefGoogle Scholar
  27. Cruz A, Vazquez L, Velez M, Perez-Gil J (2004) Effect of pulmonary surfactant protein SP-B on the micro- and nanostructure of phospholipid films. Biophys J 86:308–320PubMedCrossRefGoogle Scholar
  28. de Alba E, Weiler S, Tjandra N (2003) Solution structure of human saposin C: pH-dependent interaction with phospholipid vesicles. Biochemistry 42:14729–14740PubMedCrossRefGoogle Scholar
  29. Flach CR, Cai P, Dieudonne D, Brauner JW, Keough KM, Stewart J, Mendelsohn R (2003) Location of structural transitions in an isotopically labeled lung surfactant SP-B peptide by IRRAS. Biophys J 85:340–349PubMedCrossRefGoogle Scholar
  30. Foster CD, Zhang PX, Gonzales LW, Guttentag SH (2003) In vitro surfactant protein B deficiency inhibits lamellar body formation. Am J Respir Cell Mol Biol 29:259–266PubMedCrossRefGoogle Scholar
  31. Frey SL, Pocivavsek L, Waring AJ, Walther FJ, Hernandez-Juviel JM, Ruchala P, Lee KY (2010) Functional importance of the NH2-terminal insertion sequence of lung surfactant protein B. Am J Physiol Lung Cell Mol Physiol 298:L335–L347PubMedCrossRefGoogle Scholar
  32. Fullagar WK, Aberdeen KA, Bucknall DG, Kroon PA, Gentle IR (2003) Conformational changes in SP-B as a function of surface pressure. Biophys J 85:2624–2632PubMedCrossRefGoogle Scholar
  33. Funk CJ, Wang J, Ito Y, Travanty EA, Voelker DR, Holmes KV, Mason RJ (2011) Infection of human alveolar macrophages by coronavirus 229E. J Gen Virol 93:494–503Google Scholar
  34. Glasser SW, Burhans MS, Korfhagen TR, Na CL, Sly PD, Ross GF, Ikegami M, Whitsett JA (2001) Altered stability of pulmonary surfactant in SP-C-deficient mice. Proc Natl Acad Sci USA 98:6366–6371PubMedCrossRefGoogle Scholar
  35. Glasser SW, Detmer EA, Ikegami M, Na CL, Stahlman MT, Whitsett JA (2003) Pneumonitis and emphysema in sp-C gene targeted mice. J Biol Chem 278:14291–14298PubMedCrossRefGoogle Scholar
  36. Goerke J (1998) Pulmonary surfactant: functions and molecular composition. Biochim Biophys Acta 1408:79–89PubMedCrossRefGoogle Scholar
  37. Gomez-Gil L, Schurch D, Goormaghtigh E, Perez-Gil J (2009) Pulmonary surfactant protein SP-C counteracts the deleterious effects of cholesterol on the activity of surfactant films under physiologically relevant compression-expansion dynamics. Biophys J 97:2736–2745PubMedCrossRefGoogle Scholar
  38. Gordon LM, Horvath S, Longo ML, Zasadzinski JA, Taeusch HW, Faull K, Leung C, Waring AJ (1996) Conformation and molecular topography of the N-terminal segment of surfactant protein B in structure-promoting environments. Protein Sci 5:1662–1675PubMedCrossRefGoogle Scholar
  39. Gutsmann T, Riekens B, Bruhn H, Wiese A, Seydel U, Leippe M (2003) Interaction of amoebapores and NK-lysin with symmetric phospholipid and asymmetric lipopolysaccharide/phospholipid bilayers. Biochemistry 42:9804–9812PubMedCrossRefGoogle Scholar
  40. Haagsman HP, Diemel RV (2001) Surfactant-associated proteins: functions and structural variation. Comp Biochem Physiol A: Mol Integr Physiol 129:91–108CrossRefGoogle Scholar
  41. Halliday HL (2008) Surfactants: past, present and future. J Perinatol 28(Suppl 1):S47–S56PubMedCrossRefGoogle Scholar
  42. Hawgood S, Derrick M, Poulain F (1998) Structure and properties of surfactant protein B. Biochim Biophys Acta 1408:150–160PubMedCrossRefGoogle Scholar
  43. Hawkins CA, de Alba E, Tjandra N (2005) Solution structure of human saposin C in a detergent environment. J Mol Biol 346:1381–1392PubMedCrossRefGoogle Scholar
  44. Hecht O, Van Nuland NA, Schleinkofer K, Dingley AJ, Bruhn H, Leippe M, Grotzinger J (2004) Solution structure of the pore-forming protein of Entamoeba histolytica. J Biol Chem 279:17834–17841PubMedCrossRefGoogle Scholar
  45. Ikegami M, Takabatake N, Weaver TE (2002) Intersubunit disulfide bridge is not required for the protective role of SP-B against lung inflammation. J Appl Physiol 93:505–511PubMedGoogle Scholar
  46. Johansson J, Curstedt T (1997) Molecular structures and interactions of pulmonary surfactant components. Eur J Biochem 244:675–693PubMedCrossRefGoogle Scholar
  47. Johansson J, Curstedt T, Jornvall H (1991) Surfactant protein B: disulfide bridges, structural properties, and kringle similarities. Biochemistry 30:6917–6921PubMedCrossRefGoogle Scholar
  48. Kaznessis YN, Kim S, Larson RG (2002) Specific mode of interaction between components of model pulmonary surfactants using computer simulations. J Mol Biol 322:569–582PubMedCrossRefGoogle Scholar
  49. Kervinen J, Tobin GJ, Costa J, Waugh DS, Wlodawer A, Zdanov A (1999) Crystal structure of plant aspartic proteinase prophytepsin: inactivation and vacuolar targeting. EMBO J 18:3947–3955PubMedCrossRefGoogle Scholar
  50. Krol S, Ross M, Sieber M, Kunneke S, Galla HJ, Janshoff A (2000) Formation of three-dimensional protein-lipid aggregates in monolayer films induced by surfactant protein B. Biophys J 79:904–918PubMedCrossRefGoogle Scholar
  51. Kurutz JW, Lee KY (2002) NMR structure of lung surfactant peptide SP-B(11–25). Biochemistry 41:9627–9636PubMedCrossRefGoogle Scholar
  52. Leippe M, Bruhn H, Hecht O, Grotzinger J (2005) Ancient weapons: the three-dimensional structure of amoebapore A. Trends Parasitol 21:5–7PubMedCrossRefGoogle Scholar
  53. Leon L, Tatituri RV, Grenha R, Sun Y, Barral DC, Minnaard AJ, Bhowruth V, Veerapen N, Besra GS, Kasmar A, Peng W, Moody DB, Grabowski GA, Brenner MB (2012) Saposins utilize two strategies for lipid transfer and CD1 antigen presentation. Proc Natl Acad Sci USA 109:4357–4364PubMedCrossRefGoogle Scholar
  54. Lewis JF, Veldhuizen R (2003) The role of exogenous surfactant in the treatment of acute lung injury. Annu Rev Physiol 65:613–642PubMedCrossRefGoogle Scholar
  55. Liepinsh E, Andersson M, Ruysschaert JM, Otting G (1997) Saposin fold revealed by the NMR structure of NK-lysin. Nat Struct Biol 4:793–795PubMedCrossRefGoogle Scholar
  56. Lin S, Akinbi HT, Breslin JS, Weaver TE (1996) Structural requirements for targeting of surfactant protein B (SP-B) to secretory granules in vitro and in vivo. J Biol Chem 271:19689–19695PubMedCrossRefGoogle Scholar
  57. Liu A, Wenzel N, Qi X (2005) Role of lysine residues in membrane anchoring of saposin C. Arch Biochem Biophys 443:101–112PubMedCrossRefGoogle Scholar
  58. Madala SK, Maxfield MD, Davidson CR, Schmidt SM, Garry D, Ikegami M, Hardie WD, Glasser SW (2011) Rapamycin regulates bleomycin-induced lung damage in SP-C-deficient mice. Pulm Med 2011:653524PubMedGoogle Scholar
  59. Manzanares D, Rodriguez-Capote K, Liu S, Haines T, Ramos Y, Zhao L, Doherty-Kirby A, Lajoie G, Possmayer F (2007) Modification of tryptophan and methionine residues is implicated in the oxidative inactivation of surfactant protein B. Biochemistry 46:5604–5615PubMedCrossRefGoogle Scholar
  60. Maruscak A, Lewis JF (2006) Exogenous surfactant therapy for ARDS. Expert Opin Investig Drugs 15:47–58PubMedCrossRefGoogle Scholar
  61. Matthay MA, Zemans RL (2010) The acute respiratory distress syndrome: pathogenesis and treatment. Annu Rev Pathol 6:147–163CrossRefGoogle Scholar
  62. Melton KR, Nesslein LL, Ikegami M, Tichelaar JW, Clark JC, Whitsett JA, Weaver TE (2003) SP-B deficiency causes respiratory failure in adult mice. Am J Physiol Lung Cell Mol Physiol 285:L543–L549PubMedGoogle Scholar
  63. Meyer KC, Zimmerman JJ (2002) Inflammation and surfactant. Paediatr Respir Rev 3:308–314PubMedCrossRefGoogle Scholar
  64. Mingarro I, Lukovic D, Vilar M, Perez-Gil J (2008) Synthetic pulmonary surfactant preparations: new developments and future trends. Curr Med Chem 15:393–403PubMedCrossRefGoogle Scholar
  65. Miteva M, Andersson M, Karshikoff A, Otting G (1999) Molecular electroporation: a unifying concept for the description of membrane pore formation by antibacterial peptides, exemplified with NK-lysin. FEBS Lett 462:155–158PubMedCrossRefGoogle Scholar
  66. Morrow MR, Perez-Gil J, Simatos G, Boland C, Stewart J, Absolom D, Sarin V, Keough KM (1993) Pulmonary surfactant-associated protein SP-B has little effect on acyl chains in dipalmitoylphosphatidylcholine dispersions. Biochemistry 32:4397–4402PubMedCrossRefGoogle Scholar
  67. Morrow MR, Stewart J, Taneva S, Dico A, Keough KM (2004) Perturbation of DPPC bilayers by high concentrations of pulmonary surfactant protein SP-B. Eur Biophys J 33:285–290PubMedCrossRefGoogle Scholar
  68. Nogee LM, de Mello DE, Dehner LP, Colten HR (1993) Brief report: deficiency of pulmonary surfactant protein B in congenital alveolar proteinosis. N Engl J Med 328:406–410PubMedCrossRefGoogle Scholar
  69. Olmeda B, Garcia-Alvarez B, Cruz A, Perez-Gil J (2012) Structural and functional characterization of native complexes of pulmonary surfactant proteins purified with detergents. Biophys J 102:625a–626aCrossRefGoogle Scholar
  70. Parra E, Moleiro LH, Lopez-Montero I, Cruz A, Monroy F, Perez-Gil J (2011) A combined action of pulmonary surfactant proteins SP-B and SP-C modulates permeability and dynamics of phospholipid membranes. Biochem J 438:555–564PubMedGoogle Scholar
  71. Perez-Gil J (2008) Structure of pulmonary surfactant membranes and films: the role of proteins and lipid-protein interactions. Biochim Biophys Acta 1778:1676–1695PubMedCrossRefGoogle Scholar
  72. Perez-Gil J, Weaver TE (2010) Pulmonary surfactant pathophysiology: current models and open questions. Physiology (Bethesda) 25:132–141CrossRefGoogle Scholar
  73. Perez-Gil J, Cruz A, Casals C (1993) Solubility of hydrophobic surfactant proteins in organic solvent/water mixtures. Structural studies on SP-B and SP-C in aqueous organic solvents and lipids. Biochim Biophys Acta 1168:261–270PubMedCrossRefGoogle Scholar
  74. Piknova B, Schram V, Hall SB (2002) Pulmonary surfactant: phase behavior and function. Curr Opin Struct Biol 12:487–494PubMedCrossRefGoogle Scholar
  75. Popovic K, Holyoake J, Pomes R, Prive GG (2012) Structure of saposin A lipoprotein discs. Proc Natl Acad Sci USA 109:2908–2912PubMedCrossRefGoogle Scholar
  76. Qi X, Grabowski GA (2001) Differential membrane interactions of saposins A and C: implications for the functional specificity. J Biol Chem 276:27010–27017PubMedCrossRefGoogle Scholar
  77. Rodriguez-Capote K, Nag K, Schurch S, Possmayer F (2001) Surfactant protein interactions with neutral and acidic phospholipid films. Am J Physiol Lung Cell Mol Physiol 281:L231–L242PubMedGoogle Scholar
  78. Rossmann M, Schultz-Heienbrok R, Behlke J, Remmel N, Alings C, Sandhoff K, Saenger W, Maier T (2008) Crystal structures of human saposins C andD: implications for lipid recognition and membrane interactions. Structure 16:809–817PubMedCrossRefGoogle Scholar
  79. Rugonyi S, Biswas SC, Hall SB (2008) The biophysical function of pulmonary surfactant. Respir Physiol Neurobiol 163:244–255PubMedCrossRefGoogle Scholar
  80. Ryan MA, Qi X, Serrano AG, Ikegami M, Perez-Gil J, Johansson J, Weaver TE (2005) Mapping and analysis of the lytic and fusogenic domains of surfactant protein B. Biochemistry 44:861–872PubMedCrossRefGoogle Scholar
  81. Ryan MA, Akinbi HT, Serrano AG, Perez-Gil J, Wu H, McCormack FX, Weaver TE (2006) Antimicrobial activity of native and synthetic surfactant protein B peptides. J Immunol 176:416–425PubMedGoogle Scholar
  82. Sarker M, Waring AJ, Walther FJ, Keough KM, Booth V (2007) Structure of mini-B, a functional fragment of surfactant protein B, in detergent micelles. Biochemistry 46:11047–11056PubMedCrossRefGoogle Scholar
  83. Sarker M, Rose J, McDonald M, Morrow MR, Booth V (2011) Modifications to surfactant protein B structure and lipid interactions under respiratory distress conditions: consequences of tryptophan oxidation. Biochemistry 50:4867–4876Google Scholar
  84. Sawada K, Ariki S, Kojima T, Saito A, Yamazoe M, Nishitani C, Shimizu T, Takahashi M, Mitsuzawa H, Yokota S, Sawada N, Fujii N, Takahashi H, Kuroki Y (2010) Pulmonary collectins protect macrophages against pore-forming activity of Legionella pneumophila and suppress its intracellular growth. J Biol Chem 285:8434–8443PubMedCrossRefGoogle Scholar
  85. Schurch D, Ospina OL, Cruz A, Perez-Gil J (2010) Combined and independent action of proteins SP-B and SP-C in the surface behavior and mechanical stability of pulmonary surfactant films. Biophys J 99:3290–3299PubMedCrossRefGoogle Scholar
  86. Serrano AG, Perez-Gil J (2006) Protein-lipid interactions and surface activity in the pulmonary surfactant system. Chem Phys Lipids 141:105–118PubMedCrossRefGoogle Scholar
  87. Serrano AG, Cruz A, Rodriguez-Capote K, Possmayer F, Perez-Gil J (2005) Intrinsic structural and functional determinants within the amino acid sequence of mature pulmonary surfactant protein SP-B. Biochemistry 44:417–430PubMedCrossRefGoogle Scholar
  88. Serrano AG, Ryan M, Weaver TE, Perez-Gil J (2006) Critical structure-function determinants within the N-terminal region of pulmonary surfactant protein SP-B. Biophys J 90:238–249PubMedCrossRefGoogle Scholar
  89. Serrano AG, Cabre EJ, Perez-Gil J (2007) Identification of a segment in the precursor of pulmonary surfactant protein SP-B, potentially involved in pH-dependent membrane assembly of the protein. Biochim Biophys Acta 1768:1059–1069PubMedCrossRefGoogle Scholar
  90. Shiffer K, Hawgood S, Haagsman HP, Benson B, Clements JA, Goerke J (1993) Lung surfactant proteins, SP-B and SP-C, alter the thermodynamic properties of phospholipid membranes: a differential calorimetry study. Biochemistry 32:590–597PubMedCrossRefGoogle Scholar
  91. Stokeley D, Bemporad D, Gavaghan D, Sansom MS (2007) Conformational dynamics of a lipid-interacting protein: MD simulations of saposin B. Biochemistry 46:13573–13580PubMedCrossRefGoogle Scholar
  92. Suzuki Y, Fujita Y, Kogishi K (1989) Reconstitution of tubular myelin from synthetic lipids and proteins associated with pig pulmonary surfactant. Am Rev Respir Dis 140:75–81PubMedCrossRefGoogle Scholar
  93. Tatti M, Salvioli R, Ciaffoni F, Pucci P, Andolfo A, Amoresano A, Vaccaro AM (1999) Structural and membrane-binding properties of saposin D. Eur J Biochem 263:486–494PubMedCrossRefGoogle Scholar
  94. Vandenbussche G, Clercx A, Clercx M, Curstedt T, Johansson J, Jornvall H, Ruysschaert JM (1992) Secondary structure and orientation of the surfactant protein SP-B in a lipid environment. A Fourier transform infrared spectroscopy study. Biochemistry 31:9169–9176PubMedCrossRefGoogle Scholar
  95. Walther FJ, Waring AJ, Sherman MA, Zasadzinski JA, Gordon LM (2007) Hydrophobic surfactant proteins and their analogues. Neonatology 91:303–310PubMedCrossRefGoogle Scholar
  96. Wang Y, Rao KM, Demchuk E (2003) Topographical organization of the N-terminal segment of lung pulmonary surfactant protein B (SP-B(1–25)) in phospholipid bilayers. Biochemistry 42:4015–4027PubMedCrossRefGoogle Scholar
  97. Waring AJ, Walther FJ, Gordon LM, Hernandez-Juviel JM, Hong T, Sherman MA, Alonso C, Alig T, Braun A, Bacon D, Zasadzinski JA (2005) The role of charged amphipathic helices in the structure and function of surfactant protein B. J Pept Res 66:364–374PubMedCrossRefGoogle Scholar
  98. Wert SE, Whitsett JA, Nogee LM (2009) Genetic disorders of surfactant dysfunction. Pediatr Dev Pathol 12:253–274PubMedCrossRefGoogle Scholar
  99. Whitelegge JP, Ahn V, Norris AJ, Sung H, Waring A, Stevens RL, Fluharty CB, Prive G, Faull KF, Fluharty AL (2003) Characterization of a recombinant molecule covalently indistinguishable from human cerebroside-sulfate activator protein (CSAct or Saposin B). Cell Mol Biol (Noisy-le-grand) 49:799–807Google Scholar
  100. Whitsett JA, Wert SE, Weaver TE (2009) Alveolar surfactant homeostasis and the pathogenesis of pulmonary disease. Annu Rev Med 61:105–119CrossRefGoogle Scholar
  101. Willson DF, Notter RH (2011) The future of exogenous surfactant therapy. Respir Care 56:1369–1386 (discussion 1386–1388)PubMedCrossRefGoogle Scholar
  102. Wimley WC, White SH (1996) Experimentally determined hydrophobicity scale for proteins at membrane interfaces. Nat Struct Biol 3:842–848PubMedCrossRefGoogle Scholar
  103. Wright JR (2005) Immunoregulatory functions of surfactant proteins. Nat Rev Immunol 5:58–68PubMedCrossRefGoogle Scholar
  104. Wustneck N, Wustneck R, Perez-Gil J, Pison U (2003) Effects of oligomerization and secondary structure on the surface behavior of pulmonary surfactant proteins SP-B and SP-C. Biophys J 84:1940–1949PubMedCrossRefGoogle Scholar
  105. Yang L, Johansson J, Ridsdale R, Willander H, Fitzen M, Akinbi HT, Weaver TE (2009) Surfactant protein B propeptide contains a saposin-like protein domain with antimicrobial activity at low pH. J Immunol 184(2):975–983Google Scholar
  106. Zaltash S, Johansson J (1998) Secondary structure and limited proteolysis give experimental evidence that the precursor of pulmonary surfactant protein B contains three saposin-like domains. FEBS Lett 423:1–4PubMedCrossRefGoogle Scholar
  107. Zaltash S, Palmblad M, Curstedt T, Johansson J, Persson B (2000) Pulmonary surfactant protein B: a structural model and a functional analogue. Biochim Biophys Acta 1466:179–186PubMedCrossRefGoogle Scholar
  108. Zaltash S, Griffiths WJ, Beck D, Duan CX, Weaver TE, Johansson J (2001) Membrane activity of (Cys48Ser) lung surfactant protein B increases with dimerisation. Biol Chem 382:933–939PubMedCrossRefGoogle Scholar
  109. Zuo YY, Veldhuizen RA, Neumann AW, Petersen NO, Possmayer F (2008) Current perspectives in pulmonary surfactant–inhibition, enhancement and evaluation. Biochim Biophys Acta 1778:1947–1977PubMedCrossRefGoogle Scholar

Copyright information

© European Biophysical Societies' Association 2012

Authors and Affiliations

  • Bárbara Olmeda
    • 1
  • Begoña García-Álvarez
    • 1
  • Jesús Pérez-Gil
    • 1
  1. 1.Departamento de Bioquimica, Facultad de BiologiaUniversidad ComplutenseMadridSpain

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