RESUMEN
The prolactin receptor (PRLR) is activated by binding of prolactin in a 2:1 complex, but the activation mechanism is poorly understood. PRLR has a conserved WSXWS motif generic to cytokine class I receptors. We have determined the nuclear magnetic resonance solution structure of the membrane proximal domain of the human PRLR and find that the tryptophans of the motif adopt a T-stack conformation in the unbound state. By contrast, in the hormone bound state, a Trp/Arg-ladder is formed. The conformational change is hormone-dependent and influences the receptor-receptor dimerization site 3. In the constitutively active, breast cancer-related receptor mutant PRLR(I146L), we observed a stabilization of the dimeric state and a change in the dynamics of the motif. Here we demonstrate a structural link between the WSXWS motif, hormone binding, and receptor dimerization and propose it as a general mechanism for class 1 receptor activation.
Asunto(s)
Receptores de Citocinas/química , Receptores de Prolactina/química , Secuencias de Aminoácidos , Sitios de Unión , Dicroismo Circular , Humanos , Modelos Moleculares , Resonancia Magnética Nuclear Biomolecular , Tamaño de la Partícula , Prolactina/química , Unión Proteica , Estructura Cuaternaria de Proteína , Estructura Secundaria de Proteína , Estructura Terciaria de Proteína , VolumetríaRESUMEN
The purpose of our study was to provide descriptive data on victim and assault characteristics in sexual violence and to ascertain risk factors in the sequence of the assault events. Retrospective data were collected on all sexual assault victims presented to the sexual referral centre, the police and the Institute of Forensic Medicine in Aarhus, Denmark, during a five-year period. Four hundred and twenty-three victims were included. The annual incidence rate was 14.5 per 100,000 inhabitants aged 12-87 years and the "dark figure" was estimated to be 1.34. Median age was 21 years; 69% of the victims knew the assailant, and penile intercourse was reported in 59% of the cases. Young age and drinking alcohol were risk factors for the assault to take place in a public place. Information to high-risk groups identified by this study should be integrated in approaches of modifying sexual behaviour. Furthermore, the results from this study are useful in supporting staff and police investigators in the guidance of their efforts regarding treatment and inquiries.