| Autor: |
Alyssa D. Lokits, Julia Koehler Leman, Kristina E. Kitko, Nathan S. Alexander, Heidi E. Hamm, Jens Meiler |
| Jazyk: |
angličtina |
| Rok vydání: |
2015 |
| Předmět: |
|
| Zdroj: |
AIMS Biophysics, Vol 2, Iss 4, Pp 630-648 (2015) |
| Druh dokumentu: |
article |
| ISSN: |
2377-9098 |
| DOI: |
10.3934/biophy.2015.4.630 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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