View source for Surfactant protein B

{{Short description|Protein-coding gene in the species Homo sapiens}}
{{infobox gene}}
'''Surfactant protein B''' is an essential lipid-associated protein found in [[pulmonary surfactant]].  Without it, the [[lung]] would not be able to inflate after a deep breath out.<ref name=pmid19220077>{{cite journal | vauthors = Wert SE, Whitsett JA, Nogee LM | title = Genetic disorders of surfactant dysfunction | journal = Pediatric and Developmental Pathology | volume = 12 | issue = 4 | pages = 253–74 | year = 2009 | pmid = 19220077 | pmc = 2987676 | doi = 10.2350/09-01-0586.1 }}</ref> It rearranges [[lipid]] molecules in the fluid lining the lung so that tiny air sacs in the lung, called [[Pulmonary alveolus|alveoli]], can more easily inflate.<ref name=pmid9813296>{{cite journal | vauthors = Hawgood S, Derrick M, Poulain F | title = Structure and properties of surfactant protein B | journal = Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease | volume = 1408 | issue = 2–3 | pages = 150–60 | date = Nov 1998 | pmid = 9813296 | doi = 10.1016/S0925-4439(98)00064-7 | doi-access = free }}</ref>

== Gene ==

SP-B is encoded by ''SFTPB'', a single, 11425 [[nucleotide]] long [[gene]] on [[chromosome 2]].<ref name=EntrezGene6439/> [[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.<ref>{{cite journal | vauthors = Kattan AK, Bulagannawar PS, Malik IH | title = Congenital alveolar proteinosis | journal = Saudi Medical Journal | volume = 25 | issue = 10 | pages = 1474–7 | date = Oct 2004 | pmid = 15494826 }}</ref> 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.<ref>{{cite journal | vauthors = To KK, Zhou J, Song YQ, Hung IF, Ip WC, Cheng ZS, Chan AS, Kao RY, Wu AK, Chau S, Luk WK, Ip MS, Chan KH, Yuen KY | title = Surfactant protein B gene polymorphism is associated with severe influenza | journal = Chest | volume = 145 | issue = 6 | pages = 1237–43 | date = Jun 2014 | pmid = 24337193 | doi = 10.1378/chest.13-1651 }}</ref>

== Protein ==

Surfactant protein B (SP-B) is a small protein, weighing about 8 [[kDa]].<ref name=pmid21736957>{{cite journal | vauthors = Agostoni P, Banfi C, Magrì D, Vignati C, Doria E, Salvioni E, Moliterni P, Marenzi G, Tremoli E, Sisillo E | title = Kinetics of plasma SPB and RAGE during mechanical ventilation in patients undergoing major vascular surgery | journal = Respiratory Physiology & Neurobiology | volume = 178 | issue = 2 | pages = 256–60 | date = Sep 2011 | pmid = 21736957 | doi = 10.1016/j.resp.2011.06.019 | s2cid = 30847636 }}</ref> [[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.<ref name=pmid19220077/> In the body, two molecules of SP-B stick together and form what is called a [[homodimer]].<ref name=pmid21429235>{{cite journal | vauthors = Simonato M, Baritussio A, Ori C, Vedovelli L, Rossi S, Dalla Massara L, Rizzi S, Carnielli VP, Cogo PE | title = Disaturated-phosphatidylcholine and surfactant protein-B turnover in human acute lung injury and in control patients | journal = Respiratory Research | volume = 12 | pages = 36 | year = 2011 | issue = 1 | pmid = 21429235 | pmc = 3072954 | doi = 10.1186/1465-9921-12-36 | doi-access = free }}</ref> 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 pneumocyte]]s, 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]].<ref name=pmid19220077/> 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.<ref name=pmid21429235/>

SP-B is a [[Saposin protein domain|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.<ref name=pmid9813296/>

== 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.<ref name=pmid11181967>{{cite journal | vauthors = Weaver TE, Conkright JJ | title = Function of surfactant proteins B and C | journal = Annual Review of Physiology | volume = 63 | pages = 555–78 | year = 2001 | pmid = 11181967 | doi = 10.1146/annurev.physiol.63.1.555 }}</ref>

=== 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.<ref>{{cite journal | vauthors = Li JK | title = Comparative cardiac mechanics: Laplace's Law | journal = Journal of Theoretical Biology | volume = 118 | issue = 3 | pages = 339–43 | date = Feb 1986 | pmid = 3713216 | doi = 10.1016/S0022-5193(86)80064-9 | bibcode = 1986JThBi.118..339K }}</ref> 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|date=May 2015}}

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 ([[Dipalmitoylphosphatidylcholine]]) does not easily move to the gas/fluid interface, but SP-B helps ease and speed up this process.<ref>{{cite journal | vauthors = Schicht M, Knipping S, Hirt R, Beileke S, Sel S, Paulsen F, Bräuer L | title = Detection of surfactant proteins A, B, C, and D in human nasal mucosa and their regulation in chronic rhinosinusitis with polyps | journal = American Journal of Rhinology & Allergy | volume = 27 | issue = 1 | pages = 24–9 | date = Jan 2013 | pmid = 23406594 | doi = 10.2500/ajra.2013.27.3838 | s2cid = 34564655 }}</ref>

SP-B also indirectly reduces surface tension by organizing the lipids underneath the surface of the gas/fluid interface in structures called [[tubular myelin]].<ref name=pmid19220077/> 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.<ref name=pmid11181967/> 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 pneumocyte]]s.  Similarly to its function in organizing tubular myelin, SP-B arranges lipids into the lamellar body structure.<ref name=pmid9813296/> 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.<ref>{{cite journal | vauthors = Sarker M, Rose J, McDonald M, Morrow MR, Booth V | title = Modifications to surfactant protein B structure and lipid interactions under respiratory distress conditions: consequences of tryptophan oxidation | journal = Biochemistry | volume = 50 | issue = 1 | pages = 25–36 | date = Jan 2011 | pmid = 21128671 | doi = 10.1021/bi101426s }}</ref>

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.<ref>{{cite journal | vauthors = Cochrane CG, Revak SD | title = Pulmonary surfactant protein B (SP-B): structure-function relationships | journal = Science | volume = 254 | issue = 5031 | pages = 566–8 | date = Oct 1991 | pmid = 1948032 | doi = 10.1126/science.1948032 | bibcode = 1991Sci...254..566C }}</ref><ref>{{cite journal | vauthors = Saleem M, Meyer MC, Breitenstein D, Galla HJ | title = The surfactant peptide KL4 in lipid monolayers: phase behavior, topography, and chemical distribution | journal = The Journal of Biological Chemistry | volume = 283 | issue = 8 | pages = 5195–207 | date = Feb 2008 | pmid = 18093983 | doi = 10.1074/jbc.M705944200 | doi-access = free }}</ref>

Once lung distress has occurred, SP-B has been shown to be effective as a [[biomarker]] in the blood stream.<ref name=pmid21736957/>  Higher levels of SP-B indicate some kind of lung distress, and can even indicate if the patient is currently a smoker.<ref>{{cite journal | vauthors = Nguyen AB, Rohatgi A, Garcia CK, Ayers CR, Das SR, Lakoski SG, Berry JD, Khera A, McGuire DK, de Lemos JA | title = Interactions between smoking, pulmonary surfactant protein B, and atherosclerosis in the general population: the Dallas Heart Study | journal = Arteriosclerosis, Thrombosis, and Vascular Biology | volume = 31 | issue = 9 | pages = 2136–43 | date = Sep 2011 | pmid = 21817103 | pmc = 3177606 | doi = 10.1161/ATVBAHA.111.228692 }}</ref> 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.<ref name=pmid23069847>{{cite journal | vauthors = Silveyra P, Floros J | title = Genetic complexity of the human surfactant-associated proteins SP-A1 and SP-A2 | journal = Gene | volume = 531 | issue = 2 | pages = 126–32 | date = Dec 2013 | pmid = 23069847 | pmc = 3570704 | doi = 10.1016/j.gene.2012.09.111 }}</ref><ref name=EntrezGene6439>{{EntrezGene|6439}}</ref>  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.<ref name=pmid22201752>{{cite journal | vauthors = Silveyra P, Floros J | title = Genetic variant associations of human SP-A and SP-D with acute and chronic lung injury | journal = Frontiers in Bioscience | volume = 17 | pages = 407–29 | year = 2012 | issue = 2 | pmid = 22201752 | pmc = 3635489 | doi=10.2741/3935}}</ref> 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.  [[Infant respiratory distress syndrome|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.<ref>{{cite journal | vauthors = Lyra PP, Diniz EM, Abe-Sandes K, Angelo AL, Machado TM, Cardeal M | title = Surfactant protein B gene polymorphism in preterm babies with respiratory distress syndrome | journal = Brazilian Journal of Medical and Biological Research| volume = 44 | issue = 1 | pages = 66–72 | date = Jan 2011 | pmid = 21180884 | doi = 10.1590/s0100-879x2010007500147 | doi-access = free }}</ref>

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.<ref name=pmid9813296/> 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).<ref name=EntrezGene6439/> 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.<ref name=pmid19220077/>

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.<ref name=pmid19220077/>

SP-A and SP-D, known together as [[collectin]]s, 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.<ref name=pmid22201752/><ref name=pmid23069847/>  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|date=May 2015}}

== References ==
{{Reflist|33em}}

== External links ==
* {{MeshName|Pulmonary+Surfactant-Associated+Protein+B}}

{{Other cell membrane proteins}}

[[Category:Integral membrane proteins]]
[[Category:Lipopeptides]]
[[Category:Proteins]]
[[Category:Respiratory physiology]]
[[Category:Surfactants]]