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BIBTEX RIS

Dynamical behaviour of the human β 1 -adrenoceptor under agonist binding

2011; Taylor & Francis; Volume: 37; Issue: 11 Linguagem: Inglês

10.1080/08927022.2011.572167

1029-0435

Lucas Villas Bôas Hoelz, Rafael C. Bernardi, Bruno A. C. Horta, Jocley Queiroz Araújo, Magaly Girão Albuquerque, Fernando Moreira da Silva, Pedro G. Pascutti, Ricardo Bicca de Alencastro,

Mass Spectrometry Techniques and Applications

The human β1-adrenoceptor (hβ1AR) is a transmembrane (TM) protein responsible for the signal transduction pathway via agonist interaction. Despite its importance, hβ1AR activation mechanism is still unclear. The most studied and widely accepted mechanism is the disruption of a salt bridge between TM3 arginine and TM6 glutamic acid, called ionic lock. In this work, we constructed a functional hβ1AR-model equilibrated in a membrane environment to study the influence of agonist binding on the dynamical behaviour of hβ1AR and on the opening of the ionic lock. The results indicate that the agonist (R-noradrenaline) disturbs the hβ1AR, causing a TM helices rotation, disrupting the ionic lock. This rotational motion occurs in opposite directions in the intercellular and extracellular domains of hβ1AR, opening the ionic lock.