The initiating proteases of the complement system: controlling the cleavage

Area of Science:

• Immunology
• Biochemistry

Background:

• The complement system is integral to innate and adaptive immunity.
• Dysregulation of the complement system is implicated in various diseases.
• Three main pathways (classical, lectin, alternative) activate the complement cascade.

Purpose of the Study:

• To review the regulatory mechanisms governing complement-activating proteases.
• To elucidate the roles of C1r, C1s, and MASP-2 in complement system activation.
• To understand protease-substrate and protease-inhibitor interactions in complement regulation.

Main Methods:

• Literature review focusing on complement system proteases.
• Analysis of molecular mechanisms of protease activation and regulation.
• Examination of protease interactions with substrates and inhibitors.

Main Results:

• The classical and lectin pathways share similar protease structures and activation mechanisms.
• C1r, C1s, and MASP-2 proteases are central to initiating complement activation.
• Specific interactions with substrates and inhibitors tightly regulate protease activity.

Conclusions:

• Understanding protease regulation is key to controlling complement-mediated diseases.
• Targeting these regulatory mechanisms offers therapeutic potential.
• The review highlights conserved mechanisms in complement activation pathways.