C2 domain

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C2dom

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C2 domain

The C2 domain is a protein structural domain involved in targeting proteins to cell membranes. It is a calcium-dependent membrane-targeting module found in many different proteins, including protein kinase C (PKC), phospholipase C (PLC), and synaptotagmins. The C2 domain is typically composed of approximately 130 amino acids and is characterized by a conserved β-sandwich fold.

Structure

The C2 domain consists of eight β-strands that form a β-sandwich structure. This structure is stabilized by calcium ions, which bind to specific sites within the domain. The binding of calcium ions induces a conformational change that allows the C2 domain to interact with negatively charged phospholipid membranes.

Function

The primary function of the C2 domain is to mediate the binding of proteins to cell membranes in a calcium-dependent manner. This binding is crucial for the activation and regulation of various signaling pathways. For example, in protein kinase C, the C2 domain helps localize the enzyme to the plasma membrane, where it can phosphorylate its substrates.

Examples of Proteins with C2 Domains

• Protein kinase C (PKC)
• Phospholipase C (PLC)
• Synaptotagmins
• Ras GTPase-activating protein (RasGAP)
• Dysferlin

Role in Disease

Mutations in proteins containing C2 domains have been implicated in various diseases. For instance, mutations in the C2 domain of dysferlin are associated with limb-girdle muscular dystrophy type 2B and Miyoshi myopathy. Additionally, alterations in the C2 domain of synaptotagmin can affect neurotransmitter release, potentially leading to neurological disorders.

Research Applications

The C2 domain is a subject of extensive research due to its role in membrane targeting and signal transduction. It is often studied in the context of its interaction with phospholipids and calcium ions. Understanding the C2 domain's structure and function can provide insights into the mechanisms of various cellular processes and the development of therapeutic strategies for related diseases.

See Also

• Protein domain
• Calcium signaling
• Phospholipid
• Signal transduction