A survey of conformational and energetic changes in G protein signaling

• Published in: AIMS biophysics 2015-01, Vol.2 (4), p.630-648
• Main Authors: D. Lokits, Alyssa, Koehler Leman, Julia, E. Kitko, Kristina, S. Alexander, Nathan, E. Hamm, Heidi, Meiler, Jens
• Format: Article
• Language: English
• Subjects: energetic; G protein coupled receptor; heterotrimeric G protein; modeling; pairwise interactions; ROSETTA
• ISSN: 2377-9098; 2377-9098
• DOI: 10.3934/biophy.2015.4.630

Cell signaling is a fundamental process for all living organisms. G protein-coupled receptors (GPCRs) are a large and diverse group of transmembrane receptors which convert extracellular signals into intracellular responses primarily via coupling to heterotrimeric G proteins. In order to integrate the range of very diverse extracellular signals into a message the cell can recognize and respond to, conformational changes occur that rewire the interactions between the receptor and heterotrimer in a specific and coordinated manner. By interrogating the energetics of these interactions within the individual proteins and across protein-protein interfaces, a communication network between amino acids involved in conformational changes for signaling, is created. To construct this mapping of pairwise interactions in silico, we analyzed the Rhodopsin GPCR coupled to a Gαi1β1γ1 heterotrimer. The structure of this G protein complex was modeled in the receptor-bound and unbound heterotrimeric states as well as the activated, monomeric Gα(GTP) state. From these tertiary structural models, we computed the average pairwise residue-residue interactions and interface energies across ten models of each state using the ROSETTA modeling software suite. Here we disseminate a comprehensive survey of all critical interactions and create intra-protein network communication maps. These networks represent nodes of interaction necessary for G protein activation.