The Evolution, Oligomerization, Function, and Action Mechanism of α2-Macroglobulin

Area of Science:

• Biochemistry
• Evolutionary Biology
• Immunology

Background:

• Alpha2-macroglobulin (A2M) is a large glycoprotein belonging to the α-macroglobulin superfamily.
• It has an evolutionary origin dating back 600-700 million years, linking the α-macroglobulin family with complement components.
• A2M exhibits high structural conservation across invertebrates and vertebrates and is abundant in body fluids.

Purpose of the Study:

• To review the origin, evolution, and molecular structure of A2M.
• To summarize the principal mechanisms of A2M action and its diverse biological functions.
• To explore research progress on A2M functions in invertebrates and vertebrates and its therapeutic applications.

Main Methods:

• Literature review and synthesis of existing research on A2M.
• Analysis of structural predictions and evolutionary conservation of A2M.
• Examination of A2M's interactions with proteases, cytokines, growth factors, and receptors.

Main Results:

• A2M possesses five key functional domains governing its diverse roles.
• Its primary function involves protease entrapment and inhibition.
• A2M participates in immune responses, inflammation, hemostasis, coagulation, and disease processes.

Conclusions:

• A2M is an evolutionarily conserved molecule with multifaceted biological functions.
• Understanding A2M's structure-function relationship is crucial for exploring its therapeutic potential.
• Further research into A2M may yield novel applications for treating clinical diseases.