Conformational Dynamics of the Activated GLP-1 Receptor-G_s Complex Revealed by Cross-Linking Mass Spectrometry and Integrative Structure Modeling.

ABSTRACT: Despite advances in characterizing the structures and functions of G protein-coupled receptors (GPCRs), our understanding of GPCR activation and signaling is still limited by the lack of information on conformational dynamics. It is particularly challenging to study the dynamics of GPCR complexes with their signaling partners because of their transient nature and low stability. Here, by combining cross-linking mass spectrometry (CLMS) with integrative structure modeling, we map the conformational ensemble of an activated GPCR-G protein complex at near-atomic resolution. The integrative structures describe heterogeneous conformations for a high number of potential alternative active states of the GLP-1 receptor-G_s complex. These structures show marked differences from the previou

SUBMITTER: Yuan S 

PROVIDER: S-EPMC10214531 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature