GHKL domain

PDB 1ah6 EBI

GHKL Domain

A GHKL domain is a conserved protein domain found in a variety of proteins involved in signal transduction and DNA repair processes. The name GHKL is derived from the initials of the four protein families that contain this domain: Gyrase B, Hsp90, Histidine Kinase, and MutL. Proteins containing the GHKL domain play crucial roles in cellular functions such as DNA replication, repair, recombination, and stress response.

Structure

The GHKL domain is typically composed of approximately 200-300 amino acids and is characterized by a conserved ATP-binding motif. This motif is essential for the enzymatic activity of proteins containing the GHKL domain, as it allows them to bind and hydrolyze ATP, providing the energy necessary for their biological functions.

Function

Proteins with a GHKL domain are involved in a wide range of cellular processes. Gyrase B proteins, for example, are essential for DNA supercoiling and unwinding during DNA replication. Hsp90 proteins are molecular chaperones that assist in the folding and stabilization of client proteins. Histidine kinases are key components of two-component signal transduction systems, playing a crucial role in bacterial responses to environmental stimuli. MutL proteins are involved in DNA mismatch repair, ensuring the fidelity of DNA replication.

Role in Disease

Mutations in genes encoding proteins with a GHKL domain can lead to various diseases. For example, mutations in the human Hsp90 gene have been associated with cancer, as Hsp90 plays a critical role in the stability and function of oncoproteins. Mutations in genes encoding DNA repair proteins with a GHKL domain can result in genomic instability and predisposition to cancer.

Examples

Some well-known proteins that contain a GHKL domain include DNA gyrase B subunit, Hsp90 chaperone, EnvZ histidine kinase, and MutL DNA mismatch repair protein.

See Also

• Gyrase B
• Hsp90
• Histidine Kinase
• MutL