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Structural requirements for the neutralization of heparin-like saccharides by complement S protein/vitronectin
D A Lane1, A M Flynn, G Pejler
1Department of Haematology, Charing Cross and Westminister Medical School, London, United Kingdom.
The Journal of Biological Chemistry
|December 5, 1987
Summary
S protein/vitronectin neutralizes heparin and heparan sulfate anticoagulant activities by interacting with specific domains, including the antithrombin-binding site. This suggests a physiological role in modulating blood coagulation near the endothelium.
Area of Science:
- Biochemistry
- Molecular Biology
- Hematology
Background:
- S protein, also known as vitronectin, inhibits complement membrane attack complex assembly.
- S protein/vitronectin possesses heparin-neutralizing properties, affecting anticoagulant activities.
- Understanding the structural basis of this interaction is crucial for its physiological relevance.
Purpose of the Study:
- To investigate the structural requirements for S protein/vitronectin's heparin-neutralizing activity.
- To determine how S protein/vitronectin interacts with different heparin and heparan sulfate molecules.
- To elucidate the potential physiological role of S protein/vitronectin in modulating anticoagulant functions.
Main Methods:
- Studied neutralization of heparin, heparan sulfate, and oligosaccharides by S protein/vitronectin.
- Assessed acceleration of thrombin and Factor Xa inactivation by antithrombin.
- Utilized synthetic heparin oligosaccharides and peptides to probe binding interactions.
Main Results:
- S protein/vitronectin effectively neutralized high-affinity heparin and various oligosaccharides, including the antithrombin-binding pentasaccharide.
- Neutralization was inhibited by low-affinity heparin, suggesting interaction with proteinase binding sites.
- S protein/vitronectin neutralized heparan sulfate, similar to platelet factor 4 but unlike histidine-rich glycoprotein.
Conclusions:
- S protein/vitronectin interacts with functional domains of heparin/heparan sulfate, including the antithrombin-binding sequence.
- These interactions suggest S protein/vitronectin is a physiological modulator of anticoagulant activity.
- Potential role in regulating heparin-like molecules near the vascular endothelium.