Topological dynamics of an intrinsically disordered N-terminal domain of the human androgen receptor.

ABSTRACT: Human androgen receptor contains a large N-terminal domain (AR-NTD) that is highly dynamic and this poses a major challenge for experimental and computational analysis to decipher its conformation. Misfolding of the AR-NTD is implicated in prostate cancer and Kennedy's disease, yet our knowledge of its structure is limited to primary sequence information of the chain and a few functionally important secondary structure motifs. Here, we employed an innovative combination of molecular dynamics simulations and circuit topology (CT) analysis to identify the tertiary structure of AR-NTD. We found that the AR-NTD adopts highly dynamic loopy conformations with two identifiable regions with distinct topological make-up and dynamics. This consists of a N-terminal region (NR, residues 1-224) and a C

SUBMITTER: Sheikhhassani V 

PROVIDER: S-EPMC9134807 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature