Vitronectin binds to
integrinalpha-V beta-3 and thus promotes
cell adhesion and spreading. It also inhibits the membrane-damaging effect of the terminal cytolytic
complement pathway 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.[6] Vitronectin has been speculated to be involved in
hemostasis[8] and
tumormalignancy.[9][10]
Structure
Vitronectin is a 54 kDa glycoprotein, consisting of 478
amino acidresidues. About one-third of the protein's
molecular mass is composed of
carbohydrates. On occasion, the protein is cleaved after
arginine 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.
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.[11] Subsequently two groups reported
NMR structures of the domain.[12][13]
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[14][15][16] but this ambiguity has been resolved by the crystal structure.[16]
The somatomedin B domain of vitronectin binds to
plasminogen activator inhibitor-1 (PAI-1), and stabilizes it.[11] Thus vitronectin serves to regulate proteolysis initiated by
plasminogen activation. In addition, vitronectin is a component of
platelets 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, 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.
^Jenne D, Stanley KK (Oct 1987). "Nucleotide sequence and organization of the human S-protein gene: repeating peptide motifs in the "pexin" family and a model for their evolution". Biochemistry. 26 (21): 6735–42.
doi:
10.1021/bi00395a024.
PMID2447940.
^Felding-Habermann B, Cheresh DA (Oct 1993). "Vitronectin and its receptors". Current Opinion in Cell Biology. 5 (5): 864–8.
doi:
10.1016/0955-0674(93)90036-P.
PMID7694604.
^Kamikubo Y, De Guzman R, Kroon G, Curriden S, Neels JG, Churchill MJ, Dawson P, Ołdziej S, Jagielska A, Scheraga HA, Loskutoff DJ,
Dyson HJ (Jun 2004). "Disulfide bonding arrangements in active forms of the somatomedin B domain of human vitronectin". Biochemistry. 43 (21): 6519–34.
doi:
10.1021/bi049647c.
PMID15157085.
^
abcXu D, Baburaj K, Peterson CB, Xu Y (Aug 2001). "Model for the three-dimensional structure of vitronectin: predictions for the multi-domain protein from threading and docking". Proteins. 44 (3): 312–20.
doi:
10.1002/prot.1096.
PMID11455604.
S2CID24765480.