Vitronectin exists in two structurally and functionally distinct forms in human plasma

Area of Science:

• Biochemistry
• Cell Biology
• Hematology

Background:

• Vitronectin is a plasma glycoprotein involved in cell adhesion and regulation of complement and antithrombin III.
• Vitronectin plays a role in various physiological processes, including cell migration and tissue repair.

Purpose of the Study:

• To investigate the structural and functional heterogeneity of vitronectin in human plasma.
• To characterize the distinct forms of vitronectin and their behavior during blood coagulation.

Main Methods:

• Analysis of vitronectin in fresh human plasma using ultracentrifugation and size exclusion chromatography.
• Characterization of heparin-binding and non-heparin-binding vitronectin forms.
• Assessment of cell spreading activity and conformational properties.

Main Results:

• Fresh human plasma contains vitronectin as a heterogeneous mixture of heparin-binding (2%) and non-heparin-binding (98%) forms.
• Heparin-binding vitronectin exists as 6.5 S aggregates (5.6 nm Stokes radius) with a 65 kDa polypeptide and unfolded conformation.
• Non-heparin-binding vitronectin is a 4.2 S monomer (3.9 nm Stokes radius) with a folded conformation and cryptic site.
• Both forms mediate BHK cell spreading similarly, but blood coagulation increases heparin-binding vitronectin by over 3.5-fold.

Conclusions:

• Vitronectin exists in circulating blood in at least two structurally and functionally distinct forms.
• These distinct vitronectin forms may serve different physiological functions.
• The conversion of non-heparin-binding to heparin-binding vitronectin during coagulation suggests dynamic functional roles.