Journal: Nature Communications

Article Title: Structure of the homodimeric androgen receptor ligand-binding domain

doi: 10.1038/ncomms14388

Figure Lengend Snippet: ( a ) An UBA3 peptide comprising the canonical LxxLL motif binds tightly to AR-LBD. The results of SPR studies conducted in triplicate are shown. ( b ) Closeup around the AF-2 binding groove with the bound UBA3 peptide shown as a cartoon (pink, with leucine side chains represented as sticks). AR is also depicted as a cartoon with AF-2 and BF-3 binding areas highlighted in brighter blue and magenta, respectively, and the bound DHT moiety in sphere representation. ( c , d ) Details of the final electron density map. Most relevant AR-LBD residues are represented as sticks and H-bonds with black dotted lines. ( c ) Closeup showing major interactions across the interface of the core dimer composed by the arbitrarily labelled molecules B (in yellow) and C (in brown). Electron density is shown as either a brown or yellow mesh contoured at 1 σ . ( d ) Closeup showing docking of H6 from peripheral AR-LBD molecule A (pale blue) into the BF-3 pocket of AR-LBD molecule B (yellow). Residues from the peripheral monomer are marked with an asterisk. ( e , f ) Two views of the AR-LBD crystal structure with the four independent AR-LBD molecules ( a – d ) found in the ASU. Notice that AR-LBD monomers B (yellow) and C (brown) form a symmetrical core dimer, while the two peripheral AR-LBD labeled as ( a ) shown (teal) and ( d ) (pale blue) are associated to the BF-3 grooves of ( b , c ) respectively.

Article Snippet: A peptide corresponding to residues S 59 -V 72 of human UBA3 was custom-synthesized at Pepmic.

Techniques: Binding Assay, Labeling

Journal: Nature Communications

Article Title: Structure of the homodimeric androgen receptor ligand-binding domain

doi: 10.1038/ncomms14388

Figure Lengend Snippet: ( a ) Overall structure of the AR-LBD core dimer. The two monomers are depicted as cartoons, with monomer B (yellow) in standard orientation and monomer C in brown; helices and loops are marked. The hormone (dihydrotestosterone, DHT) and the UBA3 peptide are shown as spheres and as a cartoon, respectively. ( b ) Surface representation of the AR-LBD homodimer shown in the same orientation and coloured yellow and brown as in a . The side chains of residues involved in direct inter-monomer contacts are represented as sticks, coloured according to the monomer they belong to. The DHT moieties are depicted as color-coded spheres (oxygen, red; carbon, yellow or brown). The ‘right' AR-LBD monomer is titled by ∼20° perpendicular to the pseudo twofold axis relating the partners, which results in a slightly asymmetric dimer. ( c – e ) Closeups of the AR-LBD dimer interface highlighting major inter-domain contacts. Residues are shown as color-coded sticks (oxygen, red; nitrogen, blue; carbon, yellow or brown) and labelled. Hydrogen bonding interactions are indicated with black dots. ( f ) Closeup of the H6 helix from monomer A docking onto the BF-3 pocket of monomer B. Relevant residues are depicted as sticks and H-bonds as black dotted lines. The Tyr774* residues of the peripheral monomers occupy topologically equivalent positions as the outer ring of TRIAC ( g ) or the benzoic ring of FLF ( h ). Residues from the peripheral monomers are marked with an asterisk. See also .

Article Snippet: A peptide corresponding to residues S 59 -V 72 of human UBA3 was custom-synthesized at Pepmic.

Techniques:

Journal: Nature Communications

Article Title: Structure of the homodimeric androgen receptor ligand-binding domain

doi: 10.1038/ncomms14388

Figure Lengend Snippet: ( a ) Surface representation of the AR homodimer. The dimer interface (brown), the AF-2 groove (blue) and the BF-3 pocket (raspberry) are highlighted. Residues that form or line the LBP are shown with a Connolly dot surface and the UBA3 peptide as a pink surface. ( b ) Schematic representation of the proposed intra- and inter-domain allosteric pathways in AR-LBD. Solid arrows indicate short-range communication networks, while dashed arrows point to long-range interactions. ( c ) Close-up of the dimer interface highlighting allosteric communication between the LBPs across the dimer interface. The distances between the two R753 residues and the two DHT moieties are given.

Article Snippet: A peptide corresponding to residues S 59 -V 72 of human UBA3 was custom-synthesized at Pepmic.

Techniques: