WebPSN: a web server for high-throughput investigation of structural communication in bio-macromolecules

WebPSN: a web server for high-throughput investigation of structural communication in bio-macromolecules

Network and Atomistic Simulations Unveil the Structural Determinants of Mutations Linked to Retinal Diseases

Network and Atomistic Simulations Unveil the Structural Determinants of Mutations Linked to Retinal Diseases

A Mixed Protein Structure Network and Elastic Network Model Approach to Predict the Structural Communication in Biomolecular Systems: The PDZ2 Domain from Tyrosine Phosphatase 1E As a Case Study

A Mixed Protein Structure Network and Elastic Network Model Approach to Predict the Structural Communication in Biomolecular Systems: The PDZ2 Domain from Tyrosine Phosphatase 1E As a Case Study

Software News and Updates Wordom: A User-Friendly Program for the Analysis of Molecular Structures, Trajectories, and Free Energy Surfaces

Software News and Updates Wordom: A User-Friendly Program for the Analysis of Molecular Structures, Trajectories, and Free Energy Surfaces

Nucleotide Binding Switches the Information Flow in Ras GTPases

Nucleotide Binding Switches the Information Flow in Ras GTPases

Light on the structure of thromboxane A2 receptor heterodimers

Light on the structure of thromboxane A2 receptor heterodimers

Dimerization and ligand binding affect the structure network of A2A adenosine receptor

Dimerization and ligand binding affect the structure network of A2A adenosine receptor

Structural insights into retinitis pigmentosa from unfolding simulations of rhodopsin mutants

Structural insights into retinitis pigmentosa from unfolding simulations of rhodopsin mutants

Deciphering the Deformation Modes Associated with Function Retention and Specialization in Members of the Ras Superfamily – Structure, 2010

Deciphering the Deformation Modes Associated with Function Retention and Specialization in Members of the Ras Superfamily – Structure, 2010

Computational Screening of Rhodopsin Mutations Associated with Retinitis Pigmentosa

Computational Screening of Rhodopsin Mutations Associated with Retinitis Pigmentosa

Network-level analysis of light adaptation in rod cells under normal and altered conditions

Daniele Dell’Orco, Henning Schmidt Simona Mariania and Francesca Fanelli

Photoreceptor cells finely adjust their sensitivity and electrical response according to changes in light stimuli as a direct consequence of the feedback and regulation mechanisms in the phototransduction cascade. In this study, we employed a systems biology approach to develop a dynamic model of vertebrate rod phototransduction that accounts for the details of the underlying biochemistry. Following a bottom-up strategy, we first reproduced the results of a robust model developed by Hamer et al. (Vis. Neurosci., 2005, 22(4), 417), and then added a number of additional cascade reactions including: (a) explicit reactions to simulate the interaction between the activated effector and the regulator of G-protein signalling (RGS); (b) a reaction for the reformation of the G-protein from separate subunits; (c) a reaction for rhodopsin (R) reconstitution from the association of the opsin apoprotein with the 11-cis-retinal chromophore; (d) reactions for the slow activation of the cascade by opsin. The extended network structure successfully reproduced a number of experimental conditions that were inaccessible to prior models. With a single set of parameters the model was able to predict qualitative and quantitative features of rod photoresponses to light stimuli ranging over five orders of magnitude, in normal and altered conditions, including genetic manipulations of the cascade components. In particular, the model reproduced the salient dynamic features of the rod from Rpe65

Mol. BioSyst., 2009, 5, 1232–1246 PMID: 19756313

Mechanisms of Inter- and Intramolecular Communication in GPCRs and G Proteins

Francesco Raimondi, Michele Seeber, Pier G. De Benedetti, and Francesca Fanelli
Dulbecco Telethon Institute (DTI), and Department of Chemistry, UniVersity of Modena and Reggio Emilia, Via Campi 183, 41100 Modena, Italy

Abstract: This study represents the first attempt to couple, by computational experiments, the mechanisms of intramolecular and intermolecular communication concerning a guanidine nucleotide exchange factor (GEF), the thromboxane A2 receptor (TXA2R), and the cognate G protein (Gq) in its heterotrimeric GDP- bound state. Two-way pathways mediate the communication between the receptor-G protein interface and both the agonist binding site of the receptor and the nucleotide binding site of the G protein. The increase in solvent accessibility in the neighborhoods of the highly conserved E/DRY receptor motif, in response to agonist binding, is instrumental in favoring the penetration of the C-terminus of GqR in between the cytosolic ends of H3, H5, and H6. The arginine of the E/DRY motif is predicted to be an important mediator of the intramolecular and intermolecular communication involving the TXA2R. The receptor-G protein interface is predicted to involve multiple regions from the receptor and the G protein R-subunit. However, receptor contacts with the C-terminus of the α5-helix seem to be the major players in the receptor- catalyzed motion of the R-helical domain with respect to the Ras-like domain and in the formation of a nucleotide exit route in between the αF-helix and β6/R5 loop of Gqα. The inferences from this study are of wide interest, as they are expected to apply to the whole rhodopsin family, given also the considerable G protein promiscuity.    

J. AM. CHEM. SOC. 2008, 130, 4310-4325   PMID: 18335928