posted on 2022-02-03, 18:33authored byAlessandro Nicoli, Andreas Dunkel, Toni Giorgino, Chris de Graaf, Antonella Di Pizio
The extracellular
loop 2 (ECL2) is the longest and the most diverse
loop among class A G protein-coupled receptors (GPCRs). It connects
the transmembrane (TM) helices 4 and 5 and contains a highly conserved
cysteine through which it is bridged with TM3. In this paper, experimental
ECL2 structures were analyzed based on their sequences, shapes, and
intramolecular contacts. To take into account the flexibility, we
incorporated into our analyses information from the molecular dynamics
trajectories available on the GPCRmd website. Despite the high sequence
variability, shapes of the analyzed structures, defined by the backbone
volume overlaps, can be clustered into seven main groups. Conformational
differences within the clusters can be then identified by intramolecular
interactions with other GPCR structural domains. Overall, our work
provides a reorganization of the structural information of the ECL2
of class A GPCR subfamilies, highlighting differences and similarities
on sequence and conformation levels.