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Conformational Ensembles from Experimental Data
and Computer Simulations
Poster Abstracts
131
94-POS
Board 14
C-edge Loops of Arrestin Function as a Membrane Anchor
Ciara Lally
1
, Brian Bauer
1
, Jana Selent
2
,
Martha Sommer
1
.
1
Charité Medical University, Berlin, Germany,
2
Pompeu Fabra University, Hospital del Mar
Medical Research Institute, Barcelona, Spain.
Over 800 different G-protein-coupled receptors (GPCRs) are present in the human body and
regulate a wide variety of sensory and physiological responses. Signalling of these membrane
proteins is attenuated by a two-step mechanism entailing receptor phosphorylation by a kinase
followed by receptor binding by the protein arrestin. During formation of the arrestin–receptor
complex, arrestin interacts with the phosphorylated receptor C terminus in a pre-complex, which
activates arrestin for tight receptor binding. Although the first crystal structure of a GPCR-
arrestin complex was recently published [1], the structure of the pre-complex and how it
transitions to a high-affinity complex is poorly understood. Here we present molecular dynamics
simulations and site-directed fluorescence experiments on arrestin-1 interactions with the GPCR
rhodopsin, showing that loops within the C-edge of arrestin function as a membrane anchor.
Activation of arrestin by receptor-attached phosphates is necessary for C-edge engagement of the
membrane, and we show that these interactions are distinct in the pre-complex and high-affinity
complex in regard to their conformation and orientation. Our results expand current knowledge
of C-edge structure and further illuminate the conformational transitions that occur in arrestin
along the pathway to tight receptor binding [2].
1. Kang, Y., et al., Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser.
Nature, 2015. 523(7562): p. 561-7.
2. Lally, C.C., et al., C-edge loops of arrestin function as a membrane anchor. Nat Commun,
2017. 8: p. 14258.