Annexin

Annexins are a family of calcium-dependent phospholipid-binding proteins found in eukaryotes. They are characterized by their ability to bind to negatively charged phospholipids in a calcium-dependent manner, particularly phosphatidylserine, which is normally located on the inner leaflet of the plasma membrane.

Structure and Function:

Annexins typically consist of a highly conserved core domain composed of four or eight repeats of a characteristic ~70 amino acid sequence, known as the annexin repeat. These repeats fold into a disk-shaped structure with a convex and a concave surface. The convex surface contains the calcium and phospholipid-binding sites. The N-terminal domain is more variable and is thought to be responsible for much of the functional diversity among annexins, modulating interactions with other proteins and cellular components.

Annexins are involved in a wide range of cellular processes, including:

• Membrane Organization and Dynamics: Annexins can promote membrane aggregation, fusion, and curvature. Their ability to bind to phospholipids and calcium allows them to bridge membranes and influence their physical properties.

• Signal Transduction: Some annexins interact with signaling molecules, such as receptors and kinases, and can modulate signaling pathways.

• Inflammation: Annexins can regulate inflammatory responses by modulating the activity of inflammatory mediators and influencing leukocyte adhesion and migration.

• Apoptosis: Some annexins are involved in the regulation of programmed cell death (apoptosis).

• Exocytosis and Endocytosis: Annexins may play a role in membrane trafficking events, such as exocytosis (the release of cellular contents) and endocytosis (the uptake of material into cells).

• Blood Coagulation: Certain annexins, particularly Annexin V, exhibit anticoagulant properties and may play a role in regulating blood clotting.

Diversity:

The annexin family includes a diverse set of proteins with varying tissue distributions and functions. Different annexins may have different affinities for calcium and phospholipids, as well as different N-terminal domains that mediate specific interactions. The specific roles of each annexin depend on the cellular context and the availability of calcium and other regulatory factors.

Regulation:

The activity of annexins is regulated by several factors, including:

• Calcium Concentration: Annexin binding to phospholipids is typically calcium-dependent.

• Phosphorylation: Phosphorylation of annexins can alter their activity and localization.

• Lipid Composition: The type of phospholipids present in the membrane can influence annexin binding.

• Protein-Protein Interactions: Annexins can interact with other proteins, which can modulate their activity.

Clinical Significance:

Dysregulation of annexin expression or function has been implicated in a variety of diseases, including cancer, inflammatory disorders, and cardiovascular disease. Annexins are also potential therapeutic targets.