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A survey of conformational and energetic changes in G protein signaling

  • Received: 25 August 2015 Accepted: 26 October 2015 Published: 03 November 2015
  • 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.

    Citation: Alyssa D. Lokits, Julia Koehler Leman, Kristina E. Kitko, Nathan S. Alexander, Heidi E. Hamm, Jens Meiler. A survey of conformational and energetic changes in G protein signaling[J]. AIMS Biophysics, 2015, 2(4): 630-648. doi: 10.3934/biophy.2015.4.630

    Related Papers:

  • 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.


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