Sandbox GGC16

PU.1 is a hematopoietic transcription factor. It specifically regulates transcription of genes specific to myeloid and lymphoid cells, ultimately leading to cellular differentiation. This transcription factor binds DNA with its helix-turn-helix motif.

Name and Location

The name PU.1 comes from the protein's binding interactions with a purine-rich DNA sequence. The protein resides in the nucleus.

Binding Domain

Ets binding domain is conserved across the Ets family of proteins which consist of about 35 proteins with similar functions. Binding domain is positively charged. Residues most closely interacting with DNA include Arginine and Lysine. These are highly conserved- the two Arginines on the central helix within the major groove of the DNA and two Lysines on the outer turns.

Disease

PU.1 has been identified as an oncogene. Mutations have been identified in patients with leukemias and lymphomas. Interestingly, the mutations are not always identified within the binding site.

PEST domain

The PEST domain is adjacent to the binding domain and has been found mutated in leukemia patients. It is highly polar due to the abundance of proline, glutamate, serine, and threonine. Proteins with a PEST region typically have a short half-life of under 2 hours. It is hypothesized that the PEST region is a tag for fast degradation of the protein.

Structural highlights

This is a sample scene created with SAT to by Group, and another to make of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.