Activation Domains

The activation domains are responsible for interacting with other proteins. They are unstructured until bound by a ligand, and then they can interact with other proteins. Less sequence consensus is required for activation domains than for DNA-binding domains. Many have a high percentage of one or two particular amino acids (Asp, Glu, Gln, Pro, Ser, Thr). Acidic activation domains, which are those with Aso or Glu, are active when bound to a protein co-activator. The example we will discuss about this is the estrogen receptor.

The activation domain of the estrogen receptor has to be bound to estrogen to be in active conformation. The activation domain of the estrogen receptor is unstructured, then estrogen is bound in the pocket. The alpha helix of the receptor moves to interact with estrogen, and the other proteins move and fold, allowing the helix to contact another protein, a co-activator, which then leads to estrogen expression, also known as signalling.

Now, Tamoxifen is an antagonist or repressor in this process. When tamoxifen binds to the estrogen receptor, it blocks estrogen signals. The receptor does not undergo the necessarily structural change.

Another example is the model of the enhanceosome that forms on the B-interferon enhancer. Interferons are proteins made by host cells in response to the presence of pathogens such as viruses, bacteria, parasites, and tumour cells to signal the immune system to evoke a response.* Independent transcription factors bind together over a short sequence of the enhancer. The combination is called a multi-protein complex, which initiates transcription for a particular promotor. HMGI bends the minor groove of the DNA and then protein-protein interactions occur with highly cooperative binding to form a stable assembly of activators of transcription.

Transcription is activated through another complex known as a mediator complex, which forms a molecular bridge between the domains and Pol II to resolve the spatial separation between the activation region and promoter regions. This is a multi-protein conversation. The tail end interacts with the activation domain, and the head with Pol II. From there, transcription is initiated of the gene.

*For further details on the immune system, stay tuned! I will be covers a series of posts about the innate and adaptive immune responses including plenty of information about the roles of the various cells and their significance.