The complement system is a protein network mainly present in the blood, whose activation depends on the concerted action of serine proteases. Traditionally three distinct activation routes are considered: the classical, the lectin, and the alternative pathways. The three pathways converge at the C3 component and the cascade proceeds in a common terminal pathway.
The complement system and the different pathways were discovered from the late 19th century to the late 20th century, with the lectin pathway being the last, while the basic mechanism and components of the pathways were characterized starting from the 1950s.
Although the fundamental mechanism of the three activation routes is known, still today, there are several debated issues, like the “tick-over” activation mechanism of the alternative pathway. Nowadays more and more connections are discovered between the activation routes, and also to other proteolytic cascade systems in the blood, such as the contact and the coagulation systems, and more recently to the proprotein convertase system. Some components, like MASP-3, which had been considered as part of the lectin pathway, have a function within the alternative pathway, highlighting connections within the complement activation routes.
Regulation is also an important aspect of the complement system. In this respect, complement employs various strategies, from “traditional” regulated protease zymogen activation, and inhibition by different inhibitors, to rapid disassembly of the convertase complexes.
In this Research Topic, we focus on the latest developments regarding the activation of the complement system with mechanistic and structural implications. Special focus is attributed to how other proteolytic cascades might affect complement activation, and how the complement system influences the activation of other cascade systems.
We welcome, first of all, Review articles in connection with the topic, but Original Research papers, Opinion articles, and Mini Reviews are also welcome. We welcome submissions covering, but not limited to, the following sub-topics:
1. The latest advances regarding the mechanism of complement activation, with special emphasis on the early steps
2. Recent developments in the structural biology of complement
3. Connections to other proteolytic cascades in the blood
4. Connections within the distinct activation routes of complement
The complement system is a protein network mainly present in the blood, whose activation depends on the concerted action of serine proteases. Traditionally three distinct activation routes are considered: the classical, the lectin, and the alternative pathways. The three pathways converge at the C3 component and the cascade proceeds in a common terminal pathway.
The complement system and the different pathways were discovered from the late 19th century to the late 20th century, with the lectin pathway being the last, while the basic mechanism and components of the pathways were characterized starting from the 1950s.
Although the fundamental mechanism of the three activation routes is known, still today, there are several debated issues, like the “tick-over” activation mechanism of the alternative pathway. Nowadays more and more connections are discovered between the activation routes, and also to other proteolytic cascade systems in the blood, such as the contact and the coagulation systems, and more recently to the proprotein convertase system. Some components, like MASP-3, which had been considered as part of the lectin pathway, have a function within the alternative pathway, highlighting connections within the complement activation routes.
Regulation is also an important aspect of the complement system. In this respect, complement employs various strategies, from “traditional” regulated protease zymogen activation, and inhibition by different inhibitors, to rapid disassembly of the convertase complexes.
In this Research Topic, we focus on the latest developments regarding the activation of the complement system with mechanistic and structural implications. Special focus is attributed to how other proteolytic cascades might affect complement activation, and how the complement system influences the activation of other cascade systems.
We welcome, first of all, Review articles in connection with the topic, but Original Research papers, Opinion articles, and Mini Reviews are also welcome. We welcome submissions covering, but not limited to, the following sub-topics:
1. The latest advances regarding the mechanism of complement activation, with special emphasis on the early steps
2. Recent developments in the structural biology of complement
3. Connections to other proteolytic cascades in the blood
4. Connections within the distinct activation routes of complement
