Classification Model for the Second Extracellular Loop of Class A GPCRs

• DOI: 10.1021/acs.jcim.1c01056
• Publication Date: 2022-02-03T18:19:43Z
• Authors: Alessandro Nicoli; Andreas Dunkel; Toni Giorgino; Chris de Graaf; Antonella Di Pizio
• Keywords: Sequence (biology)

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