C3 (complement)
Encyclopedia
Complement component 3, often simply called C3, is a protein
of the immune system
. It plays a central role in the complement system
and contributes to innate immunity. In humans it is encoded on chromosome 19 by a gene
called C3.
. Its activation is required for both classical
and alternative complement activation
pathways. People with C3 deficiency are susceptible to bacterial infection.
One form of C3-convertase
, also known as C4b2a, is formed by a heterodimer of activated forms of C4 and C2. It catalyzes the proteolytic cleavage of C3 into C3a
and C3b
, generated during activation through the classical pathway as well as the mannan-binding lectin pathway
. C3a is an anaphylotoxin and the precusor of some cytokines such as ASP
, and C3b serves as an opsonizing
agent. Factor I can cleave C3b into C3c and C3d, the latter of which plays a role in enhancing B cell
responses. In the alternative complement pathway, C3 is cleaved by C3bBb, another form of C3-convertase composed of activated forms of C3 (C3b) and factor B (Bb). Once C3 is activated to C3b, it exposes a reactive thioester that allows the peptide to covalently attach to any surface that can provide a nucleophile such as a primary amine or a hydroxyl group. Activated C3 can then interact with factor B. Factor B is then activated by factor D, to form Bb. The resultant complex, C3bBb, is called the alternative pathway (AP) C3 convertase.
C3bBb is deactivated in steps. First, the proteolytic component of the convertase, Bb, is removed by complement regulatory proteins having decay accelerating factor (DAF) activity. Next, C3b is broken down progressively to first iC3b, then C3c + C3dg, and then finally C3d. Factor I is the protease that performs these cuts but it requires the help of another protein to supply what is termed cofactor activity.
may be measured to support or refute a particular medical diagnosis. For example, low C3 levels are associated with some types of kidney disease such as post-infectious glomerulonephritis
and shunt nephritis
.
with Factor H
.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
of the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
. It plays a central role in the complement system
Complement system
The complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime...
and contributes to innate immunity. In humans it is encoded on chromosome 19 by a gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
called C3.
Function
C3 plays a central role in the activation of complement systemComplement system
The complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime...
. Its activation is required for both classical
Complement system
The complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime...
and alternative complement activation
Alternative complement pathway
The alternative pathway of the complement system is an innate component of the immune system's natural defense against infections, which can operate without antibody participation....
pathways. People with C3 deficiency are susceptible to bacterial infection.
One form of C3-convertase
C3-convertase
There are two forms of C3-convertase .* The first is an enzyme composed of the C4b-C2a complex, which forms during the classical or lectin pathways of the complement system. It is formed when C1s cleaves off a small peptide fragment of C2 C2b from a membrane-bound C4b-C2a complex.* The second...
, also known as C4b2a, is formed by a heterodimer of activated forms of C4 and C2. It catalyzes the proteolytic cleavage of C3 into C3a
C3a (complement)
C3a is a one of the proteins formed by the cleavage of complement component 3; the other is C3b. It stimulates mast cell degranulation, thus triggering an immune response.C3a plays an important role in chemotaxis, though not as important a role as C5a....
and C3b
C3b
C3b is the larger of two elements formed by the cleavage of complement component 3. C3b covalently bonds to microbial cell surfaces within an organism's body. This leads to the production of surface-bound C3 convertase and thus more C3b components. Bound C3b also aids in opsonization of the microbe...
, generated during activation through the classical pathway as well as the mannan-binding lectin pathway
Mannan-binding lectin pathway
The Mannan-binding lectin pathway is similar in structure to the classical complement pathway, in that, after activation, it proceeds through the action of C4 and C2 to produce activated complement proteins further down the cascade...
. C3a is an anaphylotoxin and the precusor of some cytokines such as ASP
Acylation stimulating protein
Complement 3 through its interaction with factors B and D generates C3a. In human body, C3a is rapidily cleaved by :carboxypeptidase B or carbxyopeptidase N that remove the carboxyl-terminal :arginine to generate C3adesArg. Thus, most of plasmatic C3a is present in C3adesArg form...
, and C3b serves as an opsonizing
Opsonin
An opsonin is any molecule that targets an antigen for an immune response. However, the term is usually used in reference to molecules that act as a binding enhancer for the process of phagocytosis, especially antibodies, which coat the negatively-charged molecules on the membrane. Molecules that...
agent. Factor I can cleave C3b into C3c and C3d, the latter of which plays a role in enhancing B cell
B cell
B cells are lymphocytes that play a large role in the humoral immune response . The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells and eventually develop into memory B cells after activation by antigen interaction...
responses. In the alternative complement pathway, C3 is cleaved by C3bBb, another form of C3-convertase composed of activated forms of C3 (C3b) and factor B (Bb). Once C3 is activated to C3b, it exposes a reactive thioester that allows the peptide to covalently attach to any surface that can provide a nucleophile such as a primary amine or a hydroxyl group. Activated C3 can then interact with factor B. Factor B is then activated by factor D, to form Bb. The resultant complex, C3bBb, is called the alternative pathway (AP) C3 convertase.
C3bBb is deactivated in steps. First, the proteolytic component of the convertase, Bb, is removed by complement regulatory proteins having decay accelerating factor (DAF) activity. Next, C3b is broken down progressively to first iC3b, then C3c + C3dg, and then finally C3d. Factor I is the protease that performs these cuts but it requires the help of another protein to supply what is termed cofactor activity.
Structure
Several crystallographic structures of C3 have been determined and reveal that this protein contains 13 domains.Clinical use
Levels of C3 in the bloodBlood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
may be measured to support or refute a particular medical diagnosis. For example, low C3 levels are associated with some types of kidney disease such as post-infectious glomerulonephritis
Post-infectious glomerulonephritis
Acute proliferative glomerulonephritis is a disorder of the glomeruli , or small blood vessels in the kidneys. It is a common complication of infections, typically streptococcal skin infection rather than streptococcal pharyngitis, for which it is also known as postinfectious or poststreptococcal...
and shunt nephritis
Shunt nephritis
Shunt nephritis is a rare disease of the kidney that can occur in patients being treated for hydrocephalus with a cerebral shunt. It usually results from an infected shunt that produces a long-standing blood infection, particularly by the bacterium Staphylococcus epidermidis. Kidney disease results...
.
Interactions
Complement component 3 has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with Factor H
Factor H
Factor H is a member of the regulators of complement activation family and is a complement control protein. It is a large , soluble glycoprotein that circulates in human plasma...
.