Related Experiment Video
Updated: May 19, 2026
18:30
RNA-seq Analysis of Transcriptomes in Thrombin-treated and Control Human Pulmonary Microvascular Endothelial Cells
Published on: February 13, 2013
An ensemble view of thrombin allostery
Bernhard C Lechtenberg1, Stefan M V Freund, James A Huntington
1Cambridge Institute for Medical Research, Department of Haematology, University of Cambridge, Cambridge, CB2 0XY, UK.
Biological Chemistry
|September 5, 2012
Summary
Thrombin
Area of Science:
- Biochemistry
- Molecular Biology
- Hematology
Background:
- Thrombin is a key protease in blood coagulation, regulating clotting and thrombosis.
- Its allosteric regulation, particularly by sodium ions (Na+), has been studied for decades.
- Traditional models proposed distinct 'slow' (anticoagulant) and 'fast' (procoagulant) thrombin states.
Purpose of the Study:
- To review recent data on thrombin allosteric regulation.
- To present a dynamic view of thrombin allostery, moving beyond the static two-state model.
- To explain how ligand binding influences thrombin's conformational ensemble.
Main Methods:
- Review of recent scientific literature and data.
- Analysis of experimental evidence supporting dynamic conformational ensembles.
- Integration of new perspectives on allosteric regulation.
Main Results:
- Apo-thrombin (thrombin without ligands) exists as a zymogen-like ensemble of conformations.
- Ligand binding allosterically stabilizes specific conformations within this ensemble.
- The traditional two-state model is insufficient to describe thrombin's dynamic behavior.
Conclusions:
- Thrombin allostery is best understood as a dynamic process involving a continuum of conformational states.
- Ligand interactions modulate this ensemble, influencing thrombin's procoagulant or anticoagulant activity.
- This dynamic view refines our understanding of coagulation regulation.
Related Concept Videos
01:58Cooperative Allosteric Transitions
Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
01:58Cooperative Allosteric Transitions
Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
01:58Cooperative Allosteric Transitions
Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
01:16Clot Retraction and Fibrinolysis
After a fibrin clot is formed, the next step is clot retraction, a vital process facilitated by platelet contractile proteins, such as actin and myosin. These proteins pull the fibrin strands closer together and condense the clot. This action reduces the size of the clot, creating a smaller, denser structure that effectively seals off the damaged vessel. Clot retraction consolidates the clot and helps with wound healing by bringing the edges of the damaged blood vessel closer together.
01:17Intracellular Signaling Affects Focal Adhesions
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
01:20Extrinsic and Intrinsic Pathways of Hemostasis
Blood clotting or coagulation involves extrinsic and intrinsic pathways, which ultimately merge into the common pathway, forming a fibrin clot.
The Extrinsic Pathway
The extrinsic pathway of coagulation is typically initiated by tissue damage that exposes blood to tissue factor (TF), a protein released by the damaged tissue cells outside the blood vessels—this interaction with TF triggers biochemical reactions involving specific clotting factors. The key player here is Factor VII, which forms a...
The Extrinsic Pathway
The extrinsic pathway of coagulation is typically initiated by tissue damage that exposes blood to tissue factor (TF), a protein released by the damaged tissue cells outside the blood vessels—this interaction with TF triggers biochemical reactions involving specific clotting factors. The key player here is Factor VII, which forms a...