Serpin

Serpin is a superfamily of proteins with over 1000 members identified in both animals and plants. These proteins share a common structure and are involved in a variety of biological processes, including blood coagulation, inflammation, immune response, and cell migration. Serpins function primarily as serine protease inhibitors, controlling the activity of proteases in these critical pathways. However, some serpins have evolved to inhibit other types of proteases or have entirely different functions unrelated to protease inhibition.

Structure and Mechanism

Serpins are characterized by a conserved tertiary structure, known as the serpin fold. This fold includes three β-sheets, eight or nine α-helices, and a reactive center loop (RCL) that acts as a bait for target proteases. Upon interaction with a protease, the RCL is cleaved, triggering a significant conformational change in the serpin. This change traps the protease in a covalent complex, inhibiting its enzymatic activity. This unique mechanism is referred to as a "suicide" or "mousetrap" mechanism.

Classification

Serpins are classified into clades based on their evolutionary relationships and functional similarities. The majority of serpins are found in the extracellular matrix, but some are located intracellularly. The human genome contains 36 serpin genes, which are categorized into clades A-I. Clade A serpins, such as antithrombin and alpha-1 antitrypsin, are primarily involved in the regulation of coagulation and inflammation. Clade B serpins, including ovalbumin, are found intracellularly and have a variety of functions.

Functions

The primary role of serpins is to regulate protease activity, ensuring that processes such as coagulation and inflammation proceed in a controlled manner. For example, antithrombin inhibits thrombin and other coagulation factors to prevent excessive blood clotting. Alpha-1 antitrypsin protects tissues from enzymes released by inflammatory cells, thus preventing damage during inflammation.

Beyond protease inhibition, some serpins have roles in tumor suppression, hormone transport, and neural development. The diversity of functions highlights the importance of serpins in maintaining physiological homeostasis.

Clinical Significance

Mutations in serpin genes can lead to diseases known as serpinopathies, which are characterized by the accumulation of serpin-protease complexes. For example, mutations in the SERPINA1 gene, which encodes alpha-1 antitrypsin, can lead to alpha-1 antitrypsin deficiency. This condition results in uncontrolled elastase activity, causing lung damage and liver disease. Similarly, deficiencies in antithrombin can increase the risk of thrombosis.

Research and Therapeutic Applications

Given their central role in many biological processes, serpins are targets for therapeutic intervention. Drugs that mimic or enhance serpin activity are being developed for conditions such as thrombosis, inflammation, and cancer. Additionally, understanding the mechanisms of serpinopathies is guiding the development of treatments for these genetic disorders.

‎ ‎

---

Translate: - East Asian 中文, 日本, 한국어, South Asian हिन्दी, தமிழ், తెలుగు, Urdu, ಕನ್ನಡ, Southeast Asian Indonesian, Vietnamese, Thai, မြန်မာဘာသာ, বাংলা
European español, Deutsch, français, Greek, português do Brasil, polski, română, русский, Nederlands, norsk, svenska, suomi, Italian
Middle Eastern & African عربى, Turkish, Persian, Hebrew, Afrikaans, isiZulu, Kiswahili,
Other Bulgarian, Hungarian, Czech, Swedish, മലയാളം, मराठी, ਪੰਜਾਬੀ, ગુજરાતી, Portuguese, Ukrainian