UNASSIGNED: Gamma synuclein (ySyn), a @entity5 -specific molecular chaperone, protects @entity4041 client proteins like ERa36 and stimulates rapid membrane-initiated @entity172 signalling in @entity0 cells. However, the structural perspectives of this @entity5 -specific chaperone function of ySyn remains unclear. Hence, in this present work, we studied the conformational dynamics of ERa36 in the absence and presence of @entity4041 and ySyn. Results indicate that in a chaperone-free state, ERa36 undergoes an inter-domain movement and exposes the hydrophobic patch of residues that are responsible for binding with ubiquitin. However, independent of @entity4041 , ySyn, by establishing transient interactions, prevents @entity717 , unveils the co-activator binding groove, masks the ubiquitin-binding residues and maintains 'open' pocket conformation of @entity21244 . By doing so, ySyn effectively protects ERa36 from degradation and maintains its functional state like @entity4041 based chaperoning machinery but independent of @entity855 . Our studies also show that the ySyn protected conformation of ERa36 can effectively bind with both @entity53 (E2) and @entity25608 ( @entity25609 ). Although they exhibit unique binding modes, they maintained the functionally active conformation of ERa36. Interestingly, the molecular dynamics simulation studies showed that @entity25609 , like ySyn, prevented the interdomain movements, primes the co-activator binding groove of ERa36 for complexation with downstream signalling proteins and this mechanism explains its agonist activity and associated anti- @entity172 resistance observed in the presence of ERa36. The observed differences in the chaperoning mechanism of ySyn sheds light on its selectivity over @entity4041 in @entity5 cells, for promoting rapid protection of crucial oncogenic proteins. Based on our findings, we speculate that the compounds, which can hamper association of ySyn with ERa36 and/or can arrest ERa36 in an ubiquitin binding state, would be promising alternatives for treating ERa36 expressed @entity0 .

Structural insights into @entity5 -specific chaperoning activity of gamma synuclein in protecting XXXX receptor alpha 36 and its role in tamoxifen resistance in @entity0 .

@entity172 :: ('MESH:D004967', 'Chemical') :: ['estrogen'] @entity25609 :: ('MESH:C032278', 'Chemical') :: ['4-OHT'] @entity4041 :: ('3320', 'Gene') :: ['Hsp90'] @entity0 :: ('MESH:D001943', 'Disease') :: ['breast cancer', 'breast carcinomas'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'cancer'] @entity21244 :: ('MESH:D020192', 'Disease') :: ['LBD'] @entity25608 :: ('MESH:C016601', 'Chemical') :: ['4-hydroxy tamoxifen'] @entity53 :: ('MESH:D004958', 'Chemical') :: ['estradiol'] @entity717 :: ('MESH:D009069', 'Disease') :: ['interdomain movement'] @entity855 :: ('MESH:D000255', 'Chemical') :: ['ATP']
@entity172 :: (MESH:D004967,Chemical) :: ['estrogen']
