The Role of ICL1 and H8 in Class B1 GPCRs; Implications for Receptor Activation.

ABSTRACT: The first intracellular loop (ICL1) of G protein-coupled receptors (GPCRs) has received little attention, although there is evidence that, with the 8^th helix (H8), it is involved in early conformational changes following receptor activation as well as contacting the G protein β subunit. In class B1 GPCRs, the distal part of ICL1 contains a conserved R^12.48KLRCxR^2.46b motif that extends into the base of the second transmembrane helix; this is weakly conserved as a [R/H]^12.48KL[R/H] motif in class A GPCRs. In the current study, the role of ICL1 and H8 in signaling through cAMP, _iCa²⁺ and ERK1/2 has been examined in two class B1 GPCRs, using mutagenesis and molecular dynamics. Mutations throughout ICL1 can either enhance or dis

SUBMITTER: Winfield I 

PROVIDER: S-EPMC8796428 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature