Structural insights into “acid blobs and negative noodles” – The androgen receptor as a case study

Abstract

Androgen receptor is a transcription factor that plays a key role in prostate cancer development and progression. Its N-terminal intrinsically disordered activation domain is an example of ill- structured negatively charged "acid blob" or "negative noodle" described in 1988 by Paul B. Sigler. In his model the transcription pre-initiation complex formation relies on non-specific interactions between the "negative noodles" of the transcriptional activating proteins and hydroxyl groups of the heptapeptide repeats of the C-terminal domain in the largest subunit of RNA polymerase II. Here, we take advantage of various biophysical methods to understand the AR activation domain characteristics, its ability to undergo liquid-liquid phase separation and the importance of both for protein-protein interactions of the domain. We show relevance of the secondary structure elements in the AD function despite its general "acid blob" character.