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Protein Domains

A domain on a protein is a compactly folded region in its tertiary structure. Domains tend to be roughly 50 to 300 amino acids in length and are made by folding alpha helices, beta sheets, or a combination of the two together to form a globular unit. This folding allows the formation of multiple hydrogen bonds, which serve to stabilize the protein’s structure. Smaller proteins may contain only one domain, while larger proteins can have five or more. Domains are often connected to other domains on the protein by long stretches of polypeptide chains.

Domains can have interesting structural features, such as a region rich in acidic amino acids or have a certain shape such as a leucine zipper. They can also consist of a certain sequence of amino acids that are conserved (nearly identical) in other proteins of the same family or similar proteins in other species. Domains can also be categorized by their function, such as those that allow the protein to act as a kinase or bind a cellular membrane.

Certain domains can be cut and pasted to alter the function of a protein. For example, let’s take a protein with a transmembrane domain that allows it to bind to a membrane in the cell. If a molecular biologist removes this domain then the protein can no longer bind to the membrane. Along the same lines, if this domain is introduced into a different protein then it generally gains the ability to bind to the membrane. This process allows researchers to make unique proteins with any combination of functions.


Some important and well-studied protein domains include:

  • Kinase domain – Protein kinases are responsible for adding a phosphate group to other proteins. They contain a kinase domain that can bind both ATP and the protein substrate and helps facilitate the transfer of the phosphate group from ATP to the substrate. Some current and experimental anticancer drugs, such as Glivec, work by targeting the kinase domain of certain proteins.
  • Transmembrane domain – This domain consists of numerous hydrophobic amino acids and allows a protein to attach to lipid membranes in the cell, including the plasma, nuclear, and mitochondrial membranes.
  • Src homology domains (SH2 and SH3) –These domains are involved in the transduction of signals in the cell. SH2 domains allow certain proteins to interact with tyrosine kinase receptors that have been activated by a signal outside the cell. Other proteins then bind to the protein with the SH2 domain, propagating the signal. SH3 domains also help transmit signals, except they bind to proteins with numerous proline residues instead of tyrosine kinases.
  • Leucine zipper – Also known as a bZIP domain. It is made up of two alpha helices placed parallel to each other to form a zipper-like structure held together by leucine amino acids. This domain enables a protein to bind to DNA.
  • Zinc finger – This domain is actually known as a “motif” because it is only 21 amino acids long. The amino acids are arranged in a loop to look like a finger and there is a zinc molecule present at the “knuckle.” It is also involved in DNA binding.


Molecular Biology of the Cell, Alberts, 3rd edition, 1994.