Surfactant protein B is an essential lipid-associated protein found in

pulmonary surfactant Pulmonary surfactant is a surface-active complex of phospholipids and proteins formed by Type II cells, type II alveolar cells. The proteins and lipids that make up the surfactant have both hydrophilic and hydrophobic regions. By adsorption, adso ...

. Without it, the

lung The lungs are the primary Organ (biology), organs of the respiratory system in many animals, including humans. In mammals and most other tetrapods, two lungs are located near the Vertebral column, backbone on either side of the heart. Their ...

would not be able to inflate after a deep breath out. It rearranges

lipid Lipids are a broad group of organic compounds which include fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include storing ...

molecules in the fluid lining the lung so that tiny air sacs in the lung, called

alveoli Alveolus (; pl. alveoli, adj. alveolar) is a general anatomical term for a concave cavity or pit. Uses in anatomy and zoology * Pulmonary alveolus, an air sac in the lungs ** Alveolar cell or pneumocyte ** Alveolar duct ** Alveolar macrophage * M ...

, can more easily inflate.

Gene

SP-B is encoded by ''SFTPB'', a single, 11425

nucleotide Nucleotides are Organic compound, organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both o ...

long

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

chromosome 2 Chromosome 2 is one of the twenty-three pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 2 is the second-largest human chromosome, spanning more than 242 million base pairs and representing almost ei ...

Mutations In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosi ...

in this gene are the basis for several of the lung conditions mentioned above. Both

frameshift mutations A frameshift mutation (also called a framing error or a reading frame shift) is a genetic mutation caused by indels ( insertions or deletions) of a number of nucleotides in a DNA sequence that is not divisible by three. Due to the triplet nature ...

and several

single nucleotide polymorphisms In genetics and bioinformatics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in ...

(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. 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.

Protein

Surfactant protein B (SP-B) is a small protein, weighing about 8

kDa The dalton or unified atomic mass unit (symbols: Da or u, respectively) is a unit of mass defined as of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state and at rest. It is a non-SI unit accepted f ...

Proteins Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, re ...

are composed of building blocks called

amino acids Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the Proteinogenic amino acid, 22 α-amino acids incorporated into p ...

, and SP-B is composed of 79 of them (

Valine Valine (symbol Val or V) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α- amino group (which is in the protonated −NH3+ form under biological conditions), an α- carboxylic acid group (which is in the deproton ...

alanine Alanine (symbol Ala or A), or α-alanine, is an α-amino acid that is used in the biosynthesis of proteins. It contains an amine group and a carboxylic acid group, both attached to the central carbon atom which also carries a methyl group sid ...

phenylalanine Phenylalanine (symbol Phe or F) is an essential α-amino acid with the chemical formula, formula . It can be viewed as a benzyl group substituent, substituted for the methyl group of alanine, or a phenyl group in place of a terminal hydrogen of ...

leucine Leucine (symbol Leu or L) is an essential amino acid that is used in the biosynthesis of proteins. Leucine is an α-amino acid, meaning it contains an α-amino group (which is in the protonated −NH3+ form under biological conditions), an α-Car ...

isoleucine Isoleucine (symbol Ile or I) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form under biological conditions), an α-carboxylic acid group (which is in the depro ...

, and

tryptophan Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α-carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromat ...

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. In the body, two molecules of SP-B stick together and form what is called a

homodimer In biochemistry, a protein dimer is a macromolecular complex or protein multimer, multimer formed by two protein monomers, or single proteins, which are usually Non-covalent interaction, non-covalently bound. Many macromolecules, such as proteins ...

. These are found embedded into membranes and other lipid structures, SP-B is a highly

hydrophobic In chemistry, hydrophobicity is the chemical property of a molecule (called a hydrophobe) that is seemingly repelled from a mass of water. In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, thu ...

, avoiding contact with water. SP-B is the mature form of a large precursor protein called proSP-B. Synthesized in the

endoplasmic reticulum The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryote, eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for ...

type II pneumocyte A pulmonary alveolus (; ), also called an air sac or air space, is one of millions of hollow, distensible cup-shaped cavities in the lungs where pulmonary gas exchange takes place. Oxygen is exchanged for carbon dioxide at the blood–air bar ...

s, proSP-B weighs approximately 40 kDa and is cut down to the size of mature SP-B in the

golgi apparatus The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic Cell (biology), cells. Part of the endomembrane system in the cytoplasm, it protein targeting, packages proteins ...

through a process called

post-translational modification In molecular biology, post-translational modification (PTM) is the covalent process of changing proteins following protein biosynthesis. PTMs may involve enzymes or occur spontaneously. Proteins are created by ribosomes, which translation (biolog ...

. 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. 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 Lysis ( ; from Greek 'loosening') is the breaking down of the membrane of a cell, often by viral, enzymic, or osmotic (that is, "lytic" ) mechanisms that compromise its integrity. A fluid containing the contents of lysed cells is called a ...

(breaking) of the membrane. More well known proteins in this family include saposin-C, NK-lysin, and amoebopore.

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.

Indirect surface tension reduction

The

surface tension Surface tension is the tendency of liquid surfaces at rest to shrink into the minimum surface area possible. Surface tension (physics), tension is what allows objects with a higher density than water such as razor blades and insects (e.g. Ge ...

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. 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 A monolayer is a single, closely packed layer of entities, commonly atoms or molecules. Monolayers can also be made out of cells. ''Self-assembled monolayers'' form spontaneously on surfaces. Monolayers of layered crystals like graphene and molyb ...

) 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. 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 Dipalmitoylphosphatidylcholine (DPPC) is a phospholipid (and a lecithin) consisting of two C16 palmitic acid groups attached to a phosphatidylcholine head-group. It is the main constituent of pulmonary surfactants, which reduces the work of breath ...

) does not easily move to the gas/fluid interface, but SP-B helps ease and speed up this process. SP-B also indirectly reduces surface tension by organizing the lipids underneath the surface of the gas/fluid interface in structures called

tubular myelin Pulmonary surfactant is a surface-active complex of phospholipids and proteins formed by type II alveolar cells. The proteins and lipids that make up the surfactant have both hydrophilic and hydrophobic regions. By adsorbing to the air-water i ...

. Effectively, SP-B cuts and pastes pieces of the

lipid bilayers The lipid bilayer (or phospholipid bilayer) is a thin polar membrane made of two layers of lipid molecules. These membranes form a continuous barrier around all cells. The cell membranes of almost all organisms and many viruses are made of a l ...

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. This disruption in the cohesion of water minimizes further the surface tension at the gas/fluid interface.

Formation of lamellar bodies

Lamellar bodies In cell biology, lamellar bodies (otherwise known as lamellar granules, membrane-coating granules (MCGs), keratinosomes or Odland bodies) are secretory organelles found in Alveolar cell, type II alveolar cells in the lungs, and in keratinocytes i ...

are groups of lipids and protein that are structurally similar to tubular myelin, but are found inside instead of outside the

s. Similarly to its function in organizing tubular myelin, SP-B arranges lipids into the lamellar body structure. Basically, SP-B plays a role in the

organogenesis Organogenesis is the phase of embryonic development that starts at the end of gastrulation and continues until birth. During organogenesis, the three germ layers formed from gastrulation (the ectoderm, endoderm, and mesoderm) form the internal org ...

(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

(see below)

SP-B Deficiencies and Issues

Acute respiratory distress syndrome Acute respiratory distress syndrome (ARDS) is a type of respiratory failure characterized by rapid onset of widespread inflammation in the lungs. Symptoms include shortness of breath (dyspnea), rapid breathing (tachypnea), and bluish skin co ...

, 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. 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 Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Dalton (unit), Da or more are called proteins. Chains of fewer t ...

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. Once lung distress has occurred, SP-B has been shown to be effective as a

biomarker In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, ...

in the blood stream. Higher levels of SP-B indicate some kind of lung distress, and can even indicate if the patient is currently a smoker. This may be useful in the future to predict

atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis, characterized by development of abnormalities called lesions in walls of arteries. This is a chronic inflammatory disease involving many different cell types and is driven by eleva ...

, 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

. 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. In the absence of surfactant, the surface tension at the gas/fluid interface prevents inhalation at

standard pressure Standard temperature and pressure (STP) or standard conditions for temperature and pressure are various standard sets of conditions for experimental measurements used to allow comparisons to be made between different sets of data. The most used ...

, but surfactant minimizes surface tension to values near zero and allows for normal breathing. 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 Infant respiratory distress syndrome (IRDS), also known as surfactant deficiency disorder (SDD), and previously called hyaline membrane disease (HMD), is a syndrome in premature infants caused by developmental insufficiency of pulmonary surfacta ...

(RDS) is a particularly well-known instance of surfactant deficiency because it has a high

mortality rate Mortality rate, or death rate, is a measure of the number of deaths (in general, or due to a specific cause) in a particular Statistical population, population, scaled to the size of that population, per unit of time. Mortality rate is typically ...

among

preterm Preterm birth, also known as premature birth, is the birth of a baby at fewer than 37 weeks gestational age, as opposed to full-term delivery at approximately 40 weeks. Extreme preterm is less than 28 weeks, very early preterm birth is betwee ...

babies, a variety of other conditions are related to surfactant levels and composition. 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 Lipids are a broad group of organic compounds which include fats, waxes, sterols, fat-soluble vitamins (such as vitamins Vitamin A, A, Vitamin D, D, Vitamin E, E and Vitamin K, K), monoglycerides, diglycerides, phospholipids, and others. The fu ...

are a broad category of mid-sized molecules that are

amphipathic In chemistry, an amphiphile (), or amphipath, is a chemical compound possessing both hydrophilic (''water-loving'', polar) and lipophilic (''fat-loving'', nonpolar) properties. Such a compound is called amphiphilic or amphipathic. Amphiphilic c ...

. 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 Dipalmitoylphosphatidylcholine (DPPC) is a phospholipid (and a lecithin) consisting of two C16 palmitic acid groups attached to a phosphatidylcholine head-group. It is the main constituent of pulmonary surfactants, which reduces the work of breath ...

), 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. 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 Phosphatidylglycerol is a glycerophospholipid found in pulmonary surfactant and in the plasma membrane where it directly activates lipid-gated ion channels. The general structure of phosphatidylglycerol consists of a L-glycerol 3-phosphate backbo ...

(PG),

phosphatidylinositol Phosphatidylinositol or inositol phospholipid is a biomolecule. It was initially called "inosite" when it was discovered by Léon Maquenne and Johann Joseph von Scherer in the late 19th century. It was discovered in bacteria but later also found ...

(PI),

phosphatidylethanolamine Phosphatidylethanolamine (PE) is a class of phospholipids found in biological membranes. They are synthesized by the addition of cytidine diphosphate-ethanolamine to diglycerides, releasing cytidine monophosphate. S-Adenosyl methionine, ''S''-Ade ...

(PE), and

phosphatidylserine Phosphatidylserine (abbreviated Ptd-L-Ser or PS) is a phospholipid and is a component of the cell membrane. It plays a key role in cell cycle signaling, specifically in relation to apoptosis. It is a key pathway for viruses to enter cells via a ...

(PS).

Surfactant proteins

SP-B is one of four proteins commonly found in surfactant, the other three being

surfactant protein A Surfactant protein A is an innate immune system collectin. It is water-soluble and has collagen-like domains similar to SP-D. It is part of the innate immune system and is used to opsonize bacterial cells in the alveoli marking them for phago ...

(SP-A),

surfactant protein C Surfactant protein C (SP-C), is one of the pulmonary surfactant proteins. In humans this is encoded by the ''SFTPC'' gene. It is a membrane protein. Structure SFTPC is a 197-residue protein made up of two halves: a unique N-terminal propept ...

(SP-C), and

surfactant protein D Surfactant protein D, also known as SP-D, is a lung surfactant protein part of the collagenous family of lectins called collectin. In humans, SP-D is encoded by the ''SFTPD'' gene and is part of the innate immune system. Each SP-D subunit is com ...

(SP-D). These four are highly interconnected in their functions in surfactant. For example, though the mechanism is not yet understood, SP-B functions in the

of SP-C, and mature SP-C is not formed without SP-B. 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. SP-A and SP-D, known together as

collectin Collectins, col-lectins, (collagen-containing C-type lectins) are a part of the innate immune system. They form a sub-family of collagenous Ca2+-dependent lectins of the family of C-type lectins, which are found in animals. Collectins are soluble p ...

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. 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.

References

External links

* {{Other cell membrane proteins Integral membrane proteins Lipopeptides Proteins Respiratory physiology Surfactants