Related Experiment Video
Updated: May 20, 2026
06:45
Affinity Purification of a Fibrinolytic Enzyme from Sipunculus nudus
Published on: June 2, 2023
The X-ray crystal structure of full-length human plasminogen
Ruby H P Law1, Tom Caradoc-Davies, Nathan Cowieson
1Department of Biochemistry and Molecular Biology, Monash University, Clayton, Melbourne, VIC 3800 Australia.
Cell Reports
|July 27, 2012
Summary
The structure of closed plasminogen reveals how its domains interact to prevent activation. This finding offers insights into regulating fibrinolysis and plasminogen
Area of Science:
- Biochemistry
- Molecular Biology
- Structural Biology
Background:
- Plasminogen is the inactive precursor to plasmin, the main enzyme in fibrinolysis.
- Plasminogen circulates in a closed, inactive conformation, requiring specific interactions to become activated.
Purpose of the Study:
- To elucidate the structural basis of the closed, activation-resistant conformation of plasminogen.
- To understand how kringle domains mediate interactions and conformational changes.
Main Methods:
- X-ray crystallography to determine the structure of closed plasminogen.
- Analysis of domain interactions and the role of chloride ions.
Main Results:
- The Pan-apple (PAp) and serine protease (SP) domains, with chloride ions, stabilize the closed plasminogen conformation via interactions with kringle domains.
- Glycosylation differences affect kringle domain 3 (KR3) positioning, but the activation site remains inaccessible.
- The kringle 1 (KR1) ligand-binding site is exposed, suggesting a role in recruiting plasminogen to targets.
- The peeling of kringle 5 (KR5) from the PAp domain may initiate the conformational switch to the active form.
Conclusions:
- The detailed structure explains plasminogen's auto-inhibition mechanism.
- Understanding these structural features is crucial for developing targeted fibrinolytic therapies.
Related Concept Videos
01:09Cytoskeletal Linker Proteins - Plakins
Plakins are large proteins with binding domains for microtubules, microfilaments, intermediate filaments, and membrane-associated protein complexes at cell junctions. Plakin functions are evolutionarily conserved and are primarily involved in organizing the different components of the cytoskeleton by crosslinking them to each other and connecting them to the cell-matrix and cell adhesion complexes. They are also known to interact with signal transducers, serve as scaffolds for signaling...
02:15Protein and Protein Structure
Proteins are one of the most abundant organic molecules in living systems and have the most diverse range of functions of all macromolecules. Proteins may be structural, regulatory, contractile, or protective. They may serve in transport, storage, or membranes; or they may be toxins or enzymes. Their structures, like their functions, vary greatly. They are all, however, amino acid polymers arranged in a linear sequence.
A protein's shape is critical to its function. For example, an enzyme can...
A protein's shape is critical to its function. For example, an enzyme can...