G-CSF

Furin is a proprotein convertase enzyme that plays a critical role in the activation of a wide variety of precursor proteins by cleaving them at specific sites. It is encoded by the FURIN gene in humans and is a member of the subtilisin-like proprotein convertase family.

Structure

Furin is a type I transmembrane serine protease that is synthesized as an inactive zymogen. It undergoes autocatalytic cleavage in the endoplasmic reticulum to become active. The enzyme consists of several domains, including a pro-domain, a catalytic domain, a P-domain, and a transmembrane domain. The catalytic domain contains the active site, which is responsible for the proteolytic activity of furin.

Function

Furin is involved in the processing of a wide range of precursor proteins, including hormones, growth factors, receptors, and viral proteins. It recognizes and cleaves at the consensus sequence R-X-K/R-R, where X can be any amino acid. This cleavage is essential for the maturation and activation of many proteins.

Role in Disease

Furin has been implicated in various diseases due to its role in processing proteins that are critical for disease progression. For example, furin is involved in the activation of viral glycoproteins such as those of HIV, influenza, and SARS-CoV-2, facilitating viral entry into host cells. It is also associated with cancer progression, as it activates proteins that promote tumor growth and metastasis.

Clinical Significance

Given its role in activating pathogenic proteins, furin is a potential target for therapeutic intervention. Inhibitors of furin are being explored as treatments for viral infections and cancer. Understanding the structure and function of furin is crucial for the development of these inhibitors.

Research Directions

Current research is focused on elucidating the detailed mechanisms of furin substrate recognition and cleavage, as well as developing specific inhibitors that can block its activity without affecting other proteases. Structural studies using X-ray crystallography and cryo-electron microscopy are providing insights into the enzyme's function and potential drug-binding sites.

Also see

• Proprotein convertase
• Serine protease
• Endoplasmic reticulum
• Viral glycoprotein
• SARS-CoV-2