Vitronectin (VTN or VN) is a
glycoprotein
Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...
of the
hemopexin family which is abundantly found in serum, the
extracellular matrix and
bone. In humans it is encoded by the ''VTN''
gene.
Vitronectin binds to
integrin alpha-V beta-3 and thus promotes
cell adhesion
Cell adhesion is the process by which cells interact and attach to neighbouring cells through specialised molecules of the cell surface. This process can occur either through direct contact between cell surfaces such as cell junctions or indir ...
and spreading. It also inhibits the membrane-damaging effect of the terminal cytolytic
complement pathway
A complement is something that completes something else.
Complement may refer specifically to:
The arts
* Complement (music), an interval that, when added to another, spans an octave
** Aggregate complementation, the separation of pitch-class ...
and binds to several
serpins (serine protease inhibitors). It is a secreted protein and exists in either a single chain form or a clipped, two chain form held together by a disulfide bond.
Vitronectin has been speculated to be involved in
hemostasis and
tumor malignancy.
Structure
Vitronectin is a 54 kDa glycoprotein, consisting of 478
amino acid residues. About one-third of the protein's
molecular mass is composed of
carbohydrates. On occasion, the protein is cleaved after
arginine
Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) and both the am ...
379, to produce two-chain vitronectin, where the two parts are linked by a
disulfide bond. No high-resolution structure has been determined experimentally yet,
except for the N-terminal domain.
The protein consists of three
domains:
* The
N-terminal
The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...
Somatomedin B domain (1-39)
* A central domains with
hemopexin homology (131-342)
* A
C-terminal domain (residues 347-459) also with hemopexin homology.
Several structures has been reported for the Somatomedin B domain. The protein was initially crystallized in complex with one of its physiological binding partners: the
Plasminogen activator inhibitor-1 (PAI-1) and the structure solved for this complex.
Subsequently two groups reported
NMR structures of the domain.
The somatomedin B domain is a close-knit disulfide knot, with 4 disulfide bonds within 35 residues. Different disulfide configurations had been reported for this domain
but this ambiguity has been resolved by the crystal structure.
have been built for the central and C-terminal domains.
Function
The somatomedin B domain of vitronectin binds to
plasminogen activator inhibitor-1 (PAI-1), and stabilizes it.
Thus vitronectin serves to regulate proteolysis initiated by
plasminogen activation. In addition, vitronectin is a component of
platelets
Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby ini ...
and is, thus, involved in hemostasis. Vitronectin contains an RGD (45-47) sequence, which is a binding site for membrane-bound
integrins, e.g., the
vitronectin receptor, which serve to anchor cells to the extracellular matrix. The Somatomedin B domain interacts with the
urokinase receptor
The Urokinase receptor, also known as urokinase plasminogen activator surface receptor (uPAR) or CD87 (Cluster of Differentiation 87), is a protein encoded in humans by the PLAUR gene. It is a multidomain glycoprotein tethered to the cell membran ...
, and this interaction has been implicated in cell migration and signal transduction. High plasma levels of both PAI-1 and the urokinase receptor have been shown to correlate with a negative prognosis for cancer patients. Cell adhesion and migration are directly involved in cancer
metastasis, which provides a probable mechanistic explanation for this observation.
References
Further reading
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External links
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{{Fibrous proteins
Glycoproteins
Extracellular matrix proteins
Cell adhesion proteins
