| Surfactant protein B |
Rendering of 1DFW |
| Available structures |
| PDB |
Ortholog search: PDBe, RCSB |
| List of PDB id codes |
|
1DFW, 1KMR, 1RG3, 1RG4, 1SSZ, 2DWF, 2JOU, 2M0H, 2M1T
|
|
|
| Identifiers |
| Symbols |
SFTPB ; PSP-B; SFTB3; SFTP3; SMDP1; SP-B |
| External IDs |
OMIM: 178640 MGI: 109516 HomoloGene: 456 GeneCards: SFTPB Gene |
| Gene ontology |
| Cellular component |
• extracellular space
• lysosome
|
| Biological process |
• sphingolipid metabolic process
• respiratory gaseous exchange
• organ morphogenesis
|
| Sources: Amigo / QuickGO |
|
| RNA expression pattern |
|
|
| More reference expression data |
| Orthologs |
| Species |
Human |
Mouse |
|
| Entrez |
6439 |
20388 |
|
| Ensembl |
ENSG00000168878 |
ENSMUSG00000056370 |
|
| UniProt |
P07988 |
P50405 |
|
| RefSeq (mRNA) |
NM_000542 |
NM_001282071 |
|
| RefSeq (protein) |
NP_000533 |
NP_001269000 |
|
| Location (UCSC) |
Chr 2:
85.88 – 85.9 Mb |
Chr 6:
72.3 – 72.31 Mb |
|
| PubMed search |
[1] |
[2] |
|
|
|
Pulmonary surfactant-associated protein B is a protein that in humans is encoded by the SFTPB gene.[1][2][3]
Surfactant protein B is an essential lipid-associated protein found in lung surfactant. Without it, the lung would not be able to inflate after a deep breath out.[4] It rearranges lipid molecules in the fluid lining the lung so that tiny air sacks in the lung, called alveoli, can more easily inflate.[5]
Contents
- 1 Gene
- 2 Protein
- 3 Function
- 3.1 Indirect surface tension reduction
- 3.2 Direct surface tension reduction
- 3.3 Formation of lamellar bodies
- 3.4 SP-B Deficiencies and Issues
- 4 Context in surfactant
- 4.1 Surfactant lipids
- 4.2 Surfactant proteins
- 5 Clinical significance
- 6 See also
- 7 See also
- 8 References
- 9 Further reading
- 10 External links
Gene
SP-B is encoded by SFTPB, a single, 11425 nucleotide long gene on chromosome 2.[6] Mutations in this gene are the basis for several of the lung conditions mentioned above. Both frameshift mutations and several single nucleotide polymorphisms (SNPs) have been found correlated to a variety of lung conditions. A frame shift mutation responsible for congenital alveolar proteinosis (CAP) was identified by Kattan et al.[7] Many SNP's have been identified in relation to lung conditions. They have been correlated to severe influenza, neonatal respiratory distress syndrome, mechanical ventilation necessity, and more.[8]
Protein
Surfactant protein B (SP-B) is a small protein, weighing about 8 kDa.[9] Proteins are composed of building blocks called amino acids, and SP-B is composed of 79 of them (Valine, alanine, phenylalanine, leucine, isoleucine, and tryptophan being found in the highest levels). Nine of these carry with them a positive charge, and two carry a negative charge, leaving a protein with a net (total) charge of +7.[4] In the body, two molecules of SP-B stick together and form what is called a homodimer.[10] These are found embedded into membranes and other lipid structures, SP-B is a highly hydrophobic, avoiding contact with water.
SP-B is the mature form of a large precursor protein called proSP-B. Synthesized in the endoplasmic reticulum of type II pneumocytes, proSP-B weighs approximately 40 kDa and is cut down to the size of mature SP-B in the golgi apparatus through a process called post-translational modification.[4] ProSP-B is also created in another type of lung cell called a Club cell, but these cells are unable to edit proSP-B into SP-B.[10]
SP-B is a saposin-like protein, which is a group of related proteins known particularly for binding to membranes with negative charges and facilitating either the fusion or lysis (breaking) of the membrane. More well known proteins in this family include saposin-C, NK-lysin, and amoebopore.[5]
Function
SP-B plays a critical role in the functioning of healthy lungs, and its absence inevitably leads to lung conditions, most common of which being acute respiratory distress syndrome (ARDS). Because of this, SP-B's function has been well researched, and has been found to exist in three parts. Beyond these three functions, it is worth noting that SP-B is also thought to have some anti-inflammatory function, though it is not well defined.[11]
Indirect surface tension reduction
The surface tension at the border between the fluid lining and the inhaled gas (gas/fluid interface) in alveoli determines the motion of the alveoli as a whole. According to Lapace's Law, high surface tension in the gas/fluid interface of alveoli prevents the alveoli from inflating, which causes lung collapse.[12] lipid arrangement in the fluid lining of alveoli is the primary determining factor of this surface tension since the lipids form a thin film (monolayer) on the surface of the fluid lining at the gas/fluid interface. Different lipids allow for different ranges of motion and can be compacted different.[citation needed]
SP-B plays a role in this by selected certain lipids and inserting them into the gas/fluid interface. The lipid shown to be most needed on this surface (DPPC) does not easily move to the gas/fluid interface, but SP-B helps ease and speed up this process.[13]
SP-B also indirectly reduces surface tension by organizing the lipids underneath the surface of the gas/fluid interface in structures called tubular myelin.[4] Effectively, SP-B cuts and pastes pieces of the lipid bilayers to form the three dimensional structure of the tubular myelin. This structure is the support and lipid source for the gas/fluid interface, where surface tension is a critical factor in lung function.
Direct surface tension reduction
Beyond arranging lipids in a way that reduces surface tension, SP-B actually directly interferes with attractive forces between water molecules.[11] This disruption in the cohesion of water minimizes further the surface tension at the gas/fluid interface.
Formation of lamellar bodies
Lamellar bodies are groups of lipids and protein that are structurally similar to tubular myelin, but are found inside instead of outside the type II pneumocytes. Similarly to its function in organizing tubular myelin, SP-B arranges lipids into the lamellar body structure.[5] Basically, SP-B plays a role in the organogenesis (formation of structure) of lamellar bodies. The lamellar bodies are then secreted into the fluid lining the interior of alveoli, and become tubular myelin. This role is critical for making pulmonary surfactant (see below)
SP-B Deficiencies and Issues
Acute respiratory distress syndrome, respiratory syncytial virus infection, familial lung disease, and pneumocystis infection are examples of deficiencies in and issues with SP-B that are correlated with lung issues.[14]
Because so many lung conditions are associated with issues around SP-B, synthetic replacements have been researched, created, and manufactured. It has been shown that 21 amino acid long peptides with positive charge and intermittent hydrophobic regions mimicking SP-B can minimize surface tension at the gas/fluid interface, and surfactant replacements for surfactant deficient patients has been used to save lives.[15][16]
Once lung distress has occurred, SP-B has been shown to be effective as a biomarker in the blood stream.[9] Higher levels of SP-B indicate some kind of lung distress, and can even indicate if the patient is currently a smoker.[17] This may be useful in the future to predict atherosclerosis, a solidifying of vascular tissue that has negative effects on the heart.
Context in surfactant
SP-B is a critical protein for lung function, and is found in the context of pulmonary surfactant. Understanding surfactant is important to gaining a full understanding of SP-B. Surfactant is a mixture of lipids and proteins that coats the inside of alveoli and is essential for life due to its key role in preventing alveolar collapse at low lung volumes.[6][18] In the absence of surfactant, the surface tension at the gas/fluid interface prevents inhalation at standard pressure, but surfactant minimizes surface tension to values near zero and allows for normal breathing.[19] It is also known to have a role in both the immune response and inflammation control.
Surfactant deficiency is a common cause of respiratory disease. Respiratory distress syndrome (RDS) is a particularly well-known instance of surfactant deficiency because it has a high mortality rate among preterm babies, a variety of other conditions are related to surfactant levels and composition.[20]
Surfactant is composed of primarily lipids (90% by weight), and proteins make up only the remaining 10%. The following two sections will address the lipid and protein components respectively.
Surfactant lipids
Lipids are a broad category of mid-sized molecules that are hydrophobic or amphipathic. In surfactant, two subcategories of lipids are relevant: phospholipids and sterols. Sterols are represented by cholesterol, which has an important role in the overall structure and motion of the lipids as a whole, but is vastly outnumbered by the phospholipids in surfactant.
DPPC (dipalmitoylphosphatidylcholine), as mentioned above, is a lipid with very useful stabilizing and compacting attributes. SP-B works primarily with this lipid, and moves it to the gas/fluid interface where it minimized surface tension.[5] Essentially, DPPC is so important for lung function because it can shrink or expand to fit the space necessary, and a continually shrinking and expanding lung requires components like this.
Other lipids found commonly in surfactant include phosphatidylglycerol (PG), phosphatidylinositol (PI), phosphatidylethanolamine (PE), and phosphatidylserine (PS).
Surfactant proteins
SP-B is one of four proteins commonly found in surfactant, the other three being surfactant protein A (SP-A), surfactant protein C (SP-C), and surfactant protein D (SP-D).[6] These four are highly interconnected in their functions in surfactant. For example, though the mechanism is not yet understood, SP-B functions in the post-translational modification of SP-C, and mature SP-C is not formed without SP-B.[4]
SP-C assists in the functions of SP-B, and is most similar to SP-B of the three other surfactant proteins. It is smaller, only 35 amino acids long, and is found embedded in lipid structures much like SP-B.[4]
SP-A and SP-D, known together as colletins, are more distinct from SP-B than SP-C. They are hydrophilic, so they are found in the solution, and function in immune response instead of lipid arrangement and surface tension reduction.[18][19] SP-A is actually a name for two very similar proteins, SP-A1 and SP-A2.
Along with SP-A, B, C, and D, blood plasma proteins are found in very small quantities in surfactant as well.[citation needed]
Clinical significance
Humans and animals born with a congenital absence of SP-B suffer from intractable respiratory failure.
It is associated with Surfactant metabolism dysfunction type 1.
See also
See also
- Pulmonary surfactant#Proteins
References
- ^ Pilot-Matias TJ, Kister SE, Fox JL, Kropp K, Glasser SW, Whitsett JA (Mar 1989). "Structure and organization of the gene encoding human pulmonary surfactant proteolipid SP-B". Dna 8 (2): 75–86. doi:10.1089/dna.1.1989.8.75. PMID 2924687.
- ^ Moore KJ, D'Amore-Bruno MA, Korfhagen TR, Glasser SW, Whitsett JA, Jenkins NA et al. (Feb 1992). "Chromosomal localization of three pulmonary surfactant protein genes in the mouse". Genomics 12 (2): 388–93. doi:10.1016/0888-7543(92)90389-A. PMID 1346779.
- ^ "Entrez Gene: SFTPB surfactant, pulmonary-associated protein B".
- ^ a b c d e f Wert SE, Whitsett JA, Nogee LM (2009). "Genetic disorders of surfactant dysfunction". Pediatric and Developmental Pathology 12 (4): 253–74. doi:10.2350/09-01-0586.1. PMC 2987676. PMID 19220077.
- ^ a b c d Hawgood S, Derrick M, Poulain F (Nov 1998). "Structure and properties of surfactant protein B". Biochimica Et Biophysica Acta 1408 (2-3): 150–60. doi:10.1016/S0925-4439(98)00064-7. PMID 9813296.
- ^ a b c EntrezGene 6439
- ^ Kattan AK, Bulagannawar PS, Malik IH (Oct 2004). "Congenital alveolar proteinosis". Saudi Medical Journal 25 (10): 1474–7. PMID 15494826.
- ^ To KK, Zhou J, Song YQ, Hung IF, Ip WC, Cheng ZS et al. (Jun 2014). "Surfactant protein B gene polymorphism is associated with severe influenza". Chest 145 (6): 1237–43. doi:10.1378/chest.13-1651. PMID 24337193.
- ^ a b Agostoni P, Banfi C, Magrì D, Vignati C, Doria E, Salvioni E et al. (Sep 2011). "Kinetics of plasma SPB and RAGE during mechanical ventilation in patients undergoing major vascular surgery". Respiratory Physiology & Neurobiology 178 (2): 256–60. doi:10.1016/j.resp.2011.06.019. PMID 21736957.
- ^ a b Simonato M, Baritussio A, Ori C, Vedovelli L, Rossi S, Dalla Massara L et al. (2011). "Disaturated-phosphatidylcholine and surfactant protein-B turnover in human acute lung injury and in control patients". Respiratory Research 12: 36. doi:10.1186/1465-9921-12-36. PMC 3072954. PMID 21429235.
- ^ a b Weaver TE, Conkright JJ (2001). "Function of surfactant proteins B and C". Annual Review of Physiology 63: 555–78. doi:10.1146/annurev.physiol.63.1.555. PMID 11181967.
- ^ Li JK (Feb 1986). "Comparative cardiac mechanics: Laplace's Law". Journal of Theoretical Biology 118 (3): 339–43. doi:10.1016/S0022-5193(86)80064-9. PMID 3713216.
- ^ Schicht M, Knipping S, Hirt R, Beileke S, Sel S, Paulsen F et al. (Jan 2013). "Detection of surfactant proteins A, B, C, and D in human nasal mucosa and their regulation in chronic rhinosinusitis with polyps". American Journal of Rhinology & Allergy 27 (1): 24–9. doi:10.2500/ajra.2013.27.3838. PMID 23406594.
- ^ Sarker M, Rose J, McDonald M, Morrow MR, Booth V (Jan 2011). "Modifications to surfactant protein B structure and lipid interactions under respiratory distress conditions: consequences of tryptophan oxidation". Biochemistry 50 (1): 25–36. doi:10.1021/bi101426s. PMID 21128671.
- ^ Cochrane CG, Revak SD (Oct 1991). "Pulmonary surfactant protein B (SP-B): structure-function relationships". Science 254 (5031): 566–8. Bibcode:1991Sci...254..566C. doi:10.1126/science.1948032. PMID 1948032.
- ^ Saleem M, Meyer MC, Breitenstein D, Galla HJ (Feb 2008). "The surfactant peptide KL4 in lipid monolayers: phase behavior, topography, and chemical distribution". The Journal of Biological Chemistry 283 (8): 5195–207. doi:10.1074/jbc.M705944200. PMID 18093983.
- ^ Nguyen AB, Rohatgi A, Garcia CK, Ayers CR, Das SR, Lakoski SG et al. (Sep 2011). "Interactions between smoking, pulmonary surfactant protein B, and atherosclerosis in the general population: the Dallas Heart Study". Arteriosclerosis, Thrombosis, and Vascular Biology 31 (9): 2136–43. doi:10.1161/ATVBAHA.111.228692. PMC 3177606. PMID 21817103.
- ^ a b Silveyra P, Floros J (Dec 2013). "Genetic complexity of the human surfactant-associated proteins SP-A1 and SP-A2". Gene 531 (2): 126–32. doi:10.1016/j.gene.2012.09.111. PMC 3570704. PMID 23069847.
- ^ a b Silveyra P, Floros J (2012). "Genetic variant associations of human SP-A and SP-D with acute and chronic lung injury". Frontiers in Bioscience 17: 407–29. PMC 3635489. PMID 22201752.
- ^ Lyra PP, Diniz EM, Abe-Sandes K, Angelo AL, Machado TM, Cardeal M (Jan 2011). "Surfactant protein B gene polymorphism in preterm babies with respiratory distress syndrome". Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas / Sociedade Brasileira De Biofísica ... [Et Al.] 44 (1): 66–72. PMID 21180884.
Further reading
- Pérez-Gil J (2002). "Lipid-protein interactions of hydrophobic proteins SP-B and SP-C in lung surfactant assembly and dynamics". Pediatric Pathology & Molecular Medicine 20 (6): 445–69. doi:10.1080/15227950152625783. PMID 11699574.
- Johansson J, Curstedt T, Robertson B (2002). "Artificial surfactants based on analogues of SP-B and SP-C". Pediatric Pathology & Molecular Medicine 20 (6): 501–18. doi:10.1080/15227950152625800. PMID 11699576.
- Nogee LM (2004). "Alterations in SP-B and SP-C expression in neonatal lung disease". Annual Review of Physiology 66: 601–23. doi:10.1146/annurev.physiol.66.032102.134711. PMID 14977415.
- Voorhout WF, Veenendaal T, Haagsman HP, Weaver TE, Whitsett JA, van Golde LM et al. (Oct 1992). "Intracellular processing of pulmonary surfactant protein B in an endosomal/lysosomal compartment". The American Journal of Physiology 263 (4 Pt 1): L479–86. PMID 1415726.
- Johansson J, Jörnvall H, Curstedt T (Apr 1992). "Human surfactant polypeptide SP-B. Disulfide bridges, C-terminal end, and peptide analysis of the airway form". FEBS Letters 301 (2): 165–7. doi:10.1016/0014-5793(92)81239-I. PMID 1568474.
- Yu SH, Possmayer F (Jun 1992). "Effect of pulmonary surfactant protein B (SP-B) and calcium on phospholipid adsorption and squeeze-out of phosphatidylglycerol from binary phospholipid monolayers containing dipalmitoylphosphatidylcholine". Biochimica Et Biophysica Acta 1126 (1): 26–34. doi:10.1016/0005-2760(92)90212-e. PMID 1606172.
- Weaver TE, Whitsett JA (Aug 1989). "Processing of hydrophobic pulmonary surfactant protein B in rat type II cells". The American Journal of Physiology 257 (2 Pt 1): L100–8. PMID 2475034.
- Glasser SW, Korfhagen TR, Weaver T, Pilot-Matias T, Fox JL, Whitsett JA (Jun 1987). "cDNA and deduced amino acid sequence of human pulmonary surfactant-associated proteolipid SPL(Phe)". Proceedings of the National Academy of Sciences of the United States of America 84 (12): 4007–11. doi:10.1073/pnas.84.12.4007. PMC 305010. PMID 3035561.
- Revak SD, Merritt TA, Degryse E, Stefani L, Courtney M, Hallman M et al. (Mar 1988). "Use of human surfactant low molecular weight apoproteins in the reconstitution of surfactant biologic activity". The Journal of Clinical Investigation 81 (3): 826–33. doi:10.1172/JCI113391. PMC 442533. PMID 3343343.
- Jacobs KA, Phelps DS, Steinbrink R, Fisch J, Kriz R, Mitsock L et al. (Jul 1987). "Isolation of a cDNA clone encoding a high molecular weight precursor to a 6-kDa pulmonary surfactant-associated protein". The Journal of Biological Chemistry 262 (20): 9808–11. PMID 3597440.
- Vamvakopoulos NC, Modi WS, Floros J (1994). "Mapping the human pulmonary surfactant-associated protein B gene (SFTP3) to chromosome 2p12-->p11.2". Cytogenetics and Cell Genetics 68 (1-2): 8–10. doi:10.1159/000133878. PMID 7956367.
- Nogee LM, Garnier G, Dietz HC, Singer L, Murphy AM, deMello DE et al. (Apr 1994). "A mutation in the surfactant protein B gene responsible for fatal neonatal respiratory disease in multiple kindreds". The Journal of Clinical Investigation 93 (4): 1860–3. doi:10.1172/JCI117173. PMC 294267. PMID 8163685.
- Stuhrmann M, Bohnhorst B, Peters U, Bohle RM, Poets CF, Schmidtke J (Sep 1998). "Prenatal diagnosis of congenital alveolar proteinosis (surfactant protein B deficiency)". Prenatal Diagnosis 18 (9): 953–5. doi:10.1002/(SICI)1097-0223(199809)18:9<953::AID-PD364>3.0.CO;2-J. PMID 9793979.
- Wallot M, Wagenvoort C, deMello D, Müller KM, Floros J, Roll C (Jun 1999). "Congenital alveolar proteinosis caused by a novel mutation of the surfactant protein B gene and misalignment of lung vessels in consanguineous kindred infants". European Journal of Pediatrics 158 (6): 513–8. doi:10.1007/s004310051132. PMID 10378403.
- Tredano M, van Elburg RM, Kaspers AG, Zimmermann LJ, Houdayer C, Aymard P et al. (2000). "Compound SFTPB 1549C-->GAA (121ins2) and 457delC heterozygosity in severe congenital lung disease and surfactant protein B (SP-B) deficiency". Human Mutation 14 (6): 502–9. doi:10.1002/(SICI)1098-1004(199912)14:6<502::AID-HUMU9>3.0.CO;2-C. PMID 10571948.
- Korimilli A, Gonzales LW, Guttentag SH (Mar 2000). "Intracellular localization of processing events in human surfactant protein B biosynthesis". The Journal of Biological Chemistry 275 (12): 8672–9. doi:10.1074/jbc.275.12.8672. PMID 10722708.
- Gordon LM, Lee KY, Lipp MM, Zasadzinski JA, Walther FJ, Sherman MA et al. (Apr 2000). "Conformational mapping of the N-terminal segment of surfactant protein B in lipid using 13C-enhanced Fourier transform infrared spectroscopy". The Journal of Peptide Research 55 (4): 330–47. doi:10.1034/j.1399-3011.2000.00693.x. PMID 10798379.
- Lin Z, Pearson C, Chinchilli V, Pietschmann SM, Luo J, Pison U et al. (Sep 2000). "Polymorphisms of human SP-A, SP-B, and SP-D genes: association of SP-B Thr131Ile with ARDS". Clinical Genetics 58 (3): 181–91. doi:10.1034/j.1399-0004.2000.580305.x. PMID 11076040.
External links
- Pulmonary Surfactant-Associated Protein B at the US National Library of Medicine Medical Subject Headings (MeSH)
|
Protein: cell membrane proteins (other than Cell surface receptor, enzymes, and cytoskeleton)
|
|
| Arrestin |
|
|
| Membrane-spanning 4A |
- MS4A1
- MS4A2
- MS4A3
- MS4A4A
- MS4A4E
- MS4A5
- MS4A6A
- MS4A6E
- MS4A7
- MS4A8B
- MS4A9
- MS4A10
- MS4A12
- MS4A13
- MS4A14
- MS4A15
- MS4A18
|
|
| Myelin |
- Myelin basic protein
- Myelin proteolipid protein
- Myelin oligodendrocyte glycoprotein
- Myelin-associated glycoprotein
- Myelin protein zero
|
|
| Pulmonary surfactant |
- Pulmonary surfactant-associated protein B
- Pulmonary surfactant-associated protein C
|
|
| Tetraspanin |
- TSPAN1
- TSPAN2
- TSPAN3
- TSPAN4
- TSPAN5
- TSPAN6
- TSPAN7
- TSPAN8
- TSPAN9
- TSPAN10
- TSPAN11
- TSPAN12
- TSPAN13
- TSPAN14
- TSPAN15
- TSPAN16
- TSPAN17
- TSPAN18
- TSPAN19
- TSPAN20
- TSPAN21
- TSPAN22
- TSPAN23
- TSPAN24
- TSPAN25
- TSPAN26
- TSPAN27
- TSPAN28
- TSPAN29
- TSPAN30
- TSPAN31
- TSPAN32
- TSPAN33
- TSPAN34
|
|
| Other/ungrouped |
- Calnexin
- LDL-receptor-related protein-associated protein
- Neurofibromin 2
- Presenilin
- HFE
- Phospholipid transfer proteins
- Dysferlin
- STRC
- OTOF
|
|
|
see also other cell membrane protein disorders
|
Index of cells
|
|
| Description |
- Structure
- Organelles
- peroxisome
- cytoskeleton
- centrosome
- epithelia
- cilia
- mitochondria
- Membranes
- Membrane transport
- ion channels
- vesicular transport
- solute carrier
- ABC transporters
- ATPase
- oxidoreduction-driven
|
|
| Disease |
- Structural
- peroxisome
- cytoskeleton
- cilia
- mitochondria
- nucleus
- scleroprotein
- Membrane
- channelopathy
- solute carrier
- ATPase
- ABC transporters
- other
- extracellular ligands
- cell surface receptors
- intracellular signalling
- Vesicular transport
- Pore-forming toxins
|
|
|
![価格.com - 『本体 接続部分』 UD-301-SP-B [ブラック] の製品画像](https://1mg.info/0/o/9/1343.jpg)